ADHD medication is a big business in the world today. Annual sales of ADHD medication are projected to be 15-20 billion dollars by 2020, increasing at a rate of about 8% per year. To put this in perspective, this is similar to the value of the worldwide market for fresh vegetables
( http://siteresources.worldbank.org/INTPROSPECTS/Resources/GATChapter13.pdf ).
It is an amount of money that would pay for the salaries of
400 000 teachers, each of whom paid $50 000 per year.
A relevant article to look at about this is by Alan Schwartz, published in the New York Times in 2013:
http://www.nytimes.com/2013/12/15/health/the-selling-of-attention-deficit-disorder.html?pagewanted=all&_r=0
I am not meaning this post to be a discussion of the controversies of ADHD diagnosis. Instead, this post will focus mainly about ADHD medication. I think the rising rate of ADHD diagnosis, and the rising rate of stimulant prescription, is a very concerning trend, particularly if these diagnoses and treatments are offered without attending adequately to other biopsychosocial factors, and particularly if these treatments are being offered under the influence of un-recognized biases due to the financial power and influence of the manufacturers.
On the other hand, the rising awareness and acceptance of ADHD can allow those children, adults, and families who are dealing with ADHD-related issues to feel less stigmatized, judged, and unfairly treated. In families, knowledge and acceptance of ADHD can help child-rearing practices to be adapted, so as to avoid a harshly punitive stance towards those children with attention problems.
The newer ADHD medications are, not surprisingly, very popular, frequently prescribed, are often touted as being better than the older medications, and are listed first on medication advice guideline sheets (such as the CADDRA recommendations).
Here is a comparison of costs per day between the different ADHD drugs, looking at a typical full therapeutic dose for an adult. These cost estimates come from a site called "Pharmacy Compass" which searches for the best local prices for medications at pharmacies.
1. Newer drugs (CADDRA considers these to be the only "first line" medications):
Adderall XR 30 mg:$3.91 per day
Biphentin 80 mg:$4.36 per day
Concerta 72 mg:$5.92 per day
Vyvanse 60 mg: $5.14 per day
Strattera 100 mg: $5.51 per day
2. Older drugs (CADDRA considers these "second line"):
Dexedrine spansules 40 mg: $3.59 per day
Ritalin (methylphenidate) 60 mg: $0.81 per day
Ritalin SR 60 mg $0.66 per day
So we see that the least expensive option is methylphenidate or methylphenidate SR. Dexedrine is over 5 times as expensive. Concerta and Vyvanse are about 8 times as expensive, per day.
I mention these expense differences not necessarily in an effort to favour the cheaper medication, but rather to heighten your anticipation that there could be bias in any research results regarding these medications--especially if the research is sponsored by the manufacturers-- due to the huge profit motives involved.
It would be fair to look for studies which carefully and prospectively treat ADHD patients with Ritalin vs. one of the newer medications, in randomized comparisons.
1) Vyvanse vs. Ritalin. Almost no studies in the literature! In one study, all they looked at was whether patients stuck to a dosing regimen, in which case the Vyvanse group did "better." (http://www.ncbi.nlm.nih.gov/pubmed/23937642 ) But this measure had nothing to do with the patients actually feeling better or improving more!
A better study compared Vyvanse with Oros-MPH, a long-acting version of Ritalin (though not plain old Ritalin itself!)
[ http://www.ncbi.nlm.nih.gov/pubmed/23801529]
In this study, at first glance it certainly appears that Vyvanse is better! But looking carefully, one finds statements such as this: "At endpoint, the difference between lisdexamfetamine and OROS-MPH in the percentage of patients with an ADHD-RS-IV total score less than or equal to the mean for their age was not statistically significant." (p.747) This statement was tucked into the results section but left out of the conclusion. Looking at side-effects, we find a lower total rate of adverse effects in the Ritalin group. Reduced appetite, insomnia, and nausea were more common in the Vyvanse group. Notably, there is a long list of conflicts of interest at the end of this paper, including some of the authors being employees of the Vyvanse manufacturer, and owning stocks in the company!
In conclusion here, there is no doubt that Vyvanse is an effective medication for ADHD. The dosing regime is very convenient, which may be particularly effective and helpful for many. But it is not necessarily superior to much cheaper alternatives. For some people (including many patients I have seen), regular methylphenidate (Ritalin) allows better fine control of symptoms during the course of the day, without being "stuck" with a continuous sustained-release effect. For others, they certainly do prefer the Vyvanse. I just think that Vyvanse should not be assumed to be better, as the evidence is very weak that it is, while it is 8 times more expensive than Ritalin!
2) Concerta vs. Ritalin
http://www.ncbi.nlm.nih.gov/pubmed/11389303
This is a good early study, directly comparing the two medications, published in Pediatrics in 2001. Here is the authors' concise summary: "On virtually all measures in all settings, both drug conditions were
significantly different from placebo, and the 2 drugs were not different
from each other." The reason to choose Concerta over Ritalin would be convenience. The authors do point out that "compliance" is more likely on a long-acting formulation. But remember that "compliance" is a very, very indirect, and possibly irrelevant, measure of health and well-being!! Why is it important that there be better "compliance?" Should the only criteria not be well-being? Certainly this is not a reason to classify Concerta as "better" or "first line". Concerta is 9 times more expensive than Ritalin!
3) Adderall vs Ritalin
http://www.ncbi.nlm.nih.gov/pubmed/10103335
In this study, published in Pediatrics in 1999, Adderall comes out as looking better than Ritalin. But, once again, the study was sponsored by the manufacturer. On a close look, a couple of problems: first, the doses of the medications were fixed. The ritalin doses appear too low, so as not to match the equivalent doses of Adderall given. At this point, one would usually give Ritalin doses at least twice that of Adderall (i.e. 100% higher) but in this study the Ritalin dose was only 40% higher than the Adderall dose. In accordance with this under-dosing, the Adderall group not surprisingly had more side effects such as insomnia.
In conclusion, there is no doubt that Adderall XR is a good medication for ADHD. Many of my patients have preferred it over other alternatives. But it is not fair, once again, to assume that it is better. It does not deserve to be considered "first line" while a similarly-effective alternative that is one-sixth the cost is considered "second line."
4) Meta-analytic comparison:
Faraone and Glatt (2010) have published a good meta-analytic review paper, which is worth reading in detail, with particular attention to the data tables and graphs: http://www.ncbi.nlm.nih.gov/pubmed/20051220
In the conclusion of this paper, the authors state that they "found no significant differences between short- and long-acting stimulant medications."
Addendum: a recent Cochrane review, published in February 2016 by Punja et al., concludes that there is a lot of evidence that amphetamines reduce core symptoms of ADHD, but cause a variety of problematic side-effects. They note that there was evidence of a lot of bias in the studies they looked at, with the quality of evidence being low to very low.
Here is a direct quote from their conclusion: "This review found no evidence that supports any one amphetamine
derivative over another, and does not reveal any differences between
long-acting and short-acting amphetamine preparations."
Showing posts with label ADHD. Show all posts
Showing posts with label ADHD. Show all posts
Wednesday, March 9, 2016
Wednesday, December 9, 2015
Cochrane Review: ADHD medications have lower-quality evidence than most people believe
A new Cochrane review, published on November 25, 2015 by authors Storebø and Zwi, looked at the use of stimulants to treat childhood ADHD (specifically, methylphenidate). Their conclusions included:
1. "the low quality of the underpinning evidence means that we cannot be certain of the magnitude of the effects."
2. "the general perception of methylphenidate as an effective drug for all children with ADHD seems out of step with the new evidence."
The authors found a great deal of industry sponsorship in existing studies, and found that "all 185 trials" had a high risk of bias. I would add that more recent ADHD studies, involving newer, more expensive medications, are most likely at an even higher risk of similar biases.
In general, the weaknesses of existing data are similar to the weaknesses in much other psychiatric research: studies are usually brief, rather than long-term, despite treatments often being given for many years or permanently.
Other authors, such as Hinshaw (2015)[http://www.ncbi.nlm.nih.gov/pubmed/26262927] have reached similar conclusions, including
"the diminution of medication's initial superiority [was apparent] once the randomly assigned treatment phase turned into naturalistic follow-up. The key paradox is that while ADHD clearly responds to medication and behavioral treatment in the short term, evidence for long-term effectiveness remains elusive"
How should this information inform our understanding or management of ADHD?
First, I do not think it is necessary to stop using stimulants as a treatment. However, I do think it is necessary to step away from the assumption that long-term stimulant use is appropriate for every person with ADHD symptoms. Other ways of using stimulant medication could often be more appropriate for many, such as using stimulants sporadically, to manage attentional symptoms for brief periods of time.
The evidence also does not strongly support the long-term effectiveness of behavioural therapies. This, too, is not really surprising to me.
I think that the answer lies in moving away from a highly medicalized, reductionistic approach entirely. Phenomena such as ADHD have broad biopsychosocial underpinnings: some factors exist within the individual, while many others exist in family, social, and educational structures. In some ways this is similar to other public health issues, such as obesity or addictions: a single medication or behavioural treatment is very unlikely to be a remarkably effective strategy to help with these problems. Yet, each of these strategies has a role, provided that the role is not overvalued by those offering it. Other larger social factors are extremely important as well, including factors relating to poverty, economic equality, community supports, provision of justice & public safety, etc.
So in conclusion, I see -- not surprisingly -- that we must not have exaggerated expectations of medication for treating ADHD or any other psychiatric phenomena. I do think stimulants have an important role, however, for many people, provided that the expectations are modest, and provided that side effect risks are not discounted by an over-enthusiastic prescriber with biased beliefs about long-term effectiveness vs. risk.
It is also important not to be biased against any particular treatment. In some cases, for example, balanced medication treatment of ADHD could reduce various types of risks, including substance use problems and traffic accidents, etc. It is just that the magnitude of such protective effects are likely to be exaggerated in most practioners' minds, due to the biases described above.
As with other life issues, I believe it is necessary to have a very broad view about helping strategies, which includes other types of therapeutic support if desired, as well as attention given to community, educational, cultural, and family resources--not in isolation, but in a comprehensive and holistic way.
1. "the low quality of the underpinning evidence means that we cannot be certain of the magnitude of the effects."
2. "the general perception of methylphenidate as an effective drug for all children with ADHD seems out of step with the new evidence."
The authors found a great deal of industry sponsorship in existing studies, and found that "all 185 trials" had a high risk of bias. I would add that more recent ADHD studies, involving newer, more expensive medications, are most likely at an even higher risk of similar biases.
In general, the weaknesses of existing data are similar to the weaknesses in much other psychiatric research: studies are usually brief, rather than long-term, despite treatments often being given for many years or permanently.
Other authors, such as Hinshaw (2015)[http://www.ncbi.nlm.nih.gov/pubmed/26262927] have reached similar conclusions, including
"the diminution of medication's initial superiority [was apparent] once the randomly assigned treatment phase turned into naturalistic follow-up. The key paradox is that while ADHD clearly responds to medication and behavioral treatment in the short term, evidence for long-term effectiveness remains elusive"
How should this information inform our understanding or management of ADHD?
First, I do not think it is necessary to stop using stimulants as a treatment. However, I do think it is necessary to step away from the assumption that long-term stimulant use is appropriate for every person with ADHD symptoms. Other ways of using stimulant medication could often be more appropriate for many, such as using stimulants sporadically, to manage attentional symptoms for brief periods of time.
The evidence also does not strongly support the long-term effectiveness of behavioural therapies. This, too, is not really surprising to me.
I think that the answer lies in moving away from a highly medicalized, reductionistic approach entirely. Phenomena such as ADHD have broad biopsychosocial underpinnings: some factors exist within the individual, while many others exist in family, social, and educational structures. In some ways this is similar to other public health issues, such as obesity or addictions: a single medication or behavioural treatment is very unlikely to be a remarkably effective strategy to help with these problems. Yet, each of these strategies has a role, provided that the role is not overvalued by those offering it. Other larger social factors are extremely important as well, including factors relating to poverty, economic equality, community supports, provision of justice & public safety, etc.
So in conclusion, I see -- not surprisingly -- that we must not have exaggerated expectations of medication for treating ADHD or any other psychiatric phenomena. I do think stimulants have an important role, however, for many people, provided that the expectations are modest, and provided that side effect risks are not discounted by an over-enthusiastic prescriber with biased beliefs about long-term effectiveness vs. risk.
It is also important not to be biased against any particular treatment. In some cases, for example, balanced medication treatment of ADHD could reduce various types of risks, including substance use problems and traffic accidents, etc. It is just that the magnitude of such protective effects are likely to be exaggerated in most practioners' minds, due to the biases described above.
As with other life issues, I believe it is necessary to have a very broad view about helping strategies, which includes other types of therapeutic support if desired, as well as attention given to community, educational, cultural, and family resources--not in isolation, but in a comprehensive and holistic way.
Friday, October 22, 2010
Medications for ADHD: newspaper headline
I have just looked at a front-page newspaper article by Carolyn Abraham in The Globe and Mail (Tuesday, October 19, 2010).
The article attempts to discuss the issue of whether medications are prescribed too often, for treating supposed attention deficit disorder, particularly in male children.
This is a very serious, important question. It warrants careful analysis of the issues, and a balanced evaluation of evidence.
Unfortunately, the article bothered me greatly, because of its bias. Here are some quotes from the article:
The article mentions important issues of concern, including the role of pharmaceutical marketing in changing medication prescription patterns. The diagnosis of ADHD, and the use of medications, appears to vary substantially from one locale to the next. The phenomenon of teachers coercing parents to seek medication treatment for their children is certainly problematic.
But the article did not give a balanced presentation of evidence.
It is more common, in my experience, to encounter young adults who have struggled with ADHD symptoms, without any medication treatment, all their lives. Often times, they, or their parents, have been strongly opposed to the idea of taking medications. Many of these young adults are very intelligent, but often have been unable to sit through the intellectual tasks required to develop their intelligence. Therefore, they have often not been able to achieve the goals which are reasonably available to them. There is really no way around the fact that reading, for example, is necessary to develop one's mind in the modern world; reading requires one to sit still and focus for extended periods of time. A great deal of the discipline required to develop one's intellect requires prolonged focus, often with tasks that are initially perceived to be uninteresting (with discipline, intelligence, and imagination, any so-called "boring" subject can become interesting--but if individuals are unable to focus during the initial "boring" introduction to a subject, this deep interest and engagement may never be found).
Treating ADHD with medication does not increase substance abuse. Rates of substance use in an untreated ADHD population are substantially higher. Here is a reference to a research article demonstrating this: http://www.ncbi.nlm.nih.gov/pubmed/18838643 It is certainly my clinical experience, that subjects with untreated ADHD have much higher rates of substance use, including cigarettes, alcohol, cannabis, and harder drugs. The belief that treating ADHD with medications somehow increases risk for substance abuse, is simply unfounded--the opposite effect has been clearly shown. Exceptions exist, of course, in individual cases where adolescents may be abusing their medication, selling it, etc. Also, in many cases "ADHD" is not the only issue or problem; there may be antisocial behaviour, mood disorders, severe family or psychosocial problems, etc. which also obviously affect risks.
In terms of dangers or risks, it is of course important to examine negative side-effects or toxicity from stimulants. Such an analysis would fairly establish that risks are present, but of low incidence. For example, the risk of stimulants causing heart problems.
But a fair assessment of risk must include consideration of the risks of non-treatment! The obvious risks in an ADHD population are higher risks of accidental injuries, car accidents, sequelae from substance abuse, and reckless interpersonal behaviour. The risk pertains not only to those with untreated ADHD, but also to peers (for example, passengers in a vehicle). Here are a few references evidence about this:
http://www.ncbi.nlm.nih.gov/pubmed/19739058
http://www.ncbi.nlm.nih.gov/pubmed/18815438
http://www.ncbi.nlm.nih.gov/pubmed/10790000
It is also, of course, very important to consider whether counseling or other types of therapy could be helpful for ADHD symptoms. The prevailing evidence shows that there can be small effects with existing therapy styles--this is certainly worth pursuing--but counseling often doesn't work very well. In cases where there are multiple other problems going on (e.g. anxiety, mood, family conflicts, etc.) then of course some type of external counseling support would be preferable to simply obtaining a stimulant prescription. The notion that "a few months of counseling" would make much of a difference for most kids with ADHD symptoms is absurd, and entirely unsupported by any evidence.
The idea of accepting that "that's what boys do," etc. is important to consider. But imagine, as an adult reader, that you are transported to elementary school again. Would it be a pleasant and rewarding situation for you to be in a classroom where the attitude "that's what boys do" prevails? Similar philosophies, in the adult world, have been used to justify various types of antisocial behaviour. The issue is not just about the individuals with so-called ADHD, but also about peers and community. Rambunctiousness need not be pathologized, but a desire for sustained attentiveness need not be pathologized either. Most people with ADHD histories have had serious difficulties not just in classroom settings, but in all spheres of life: home, friendships, community, work, etc. This issue is not just about artificially forcing people into the constraints of a boring, quiet classroom, although admittedly a sedate classroom environment could be a very unhelpful factor for some.
The article seems to suggest that male teachers would be preferable. What does this have to do with anything? Where is the evidence?! Is this claim not an insult to female teachers? And, in my memory, I don't remember male teachers being any better at managing a classroom of rambunctious kids, compared to female teachers. In fact, I can think of counterexamples, in which female teachers could have a gentle, maternal effect on hyperactive kids helping them to enjoy their day, so that their experience of a classroom could be more positive.
I do agree that there are learning or educational styles which could suit some individuals much better. And I agree that having opportunities to be physically active is extremely important--for everyone, not just for "ADHD kids." One of the authors in this article suggests that the decline of opportunities such as "wood shop" (the implication is, that these are mainly for boys) is part of the problem. But, imagine as a wood shop teacher -- where you are in charge of a band saw, a lathe, and a few power nail guns -- that you have a few kids who are easily bored, highly rambunctious, and have difficulty paying attention. Band saw + ADHD! Do you see any problems there?
Some "alternative learning styles" could already begin to produce an unnecessary tier, sending kids with more ADHD symptoms away from a more scholarly focus, towards developing a more physical trade. I don't think there's anything wrong with this per se, unless the child with ADHD symptoms actually wants to develop scholarly pursuits, and/or has an undeveloped talent for the type of scholarship which requires intense focus, and doesn't really want to be "tiered" in this way.
I recognize that this is an important issue, and everyone's point of view needs to be considered to work out the best solutions for health policy and for helping individuals. But this article, in one of Canada's leading newspapers, was disturbingly one-sided, and in my opinion could contribute to many individuals feeling stigmatized or rejecting the possibility of medication therapy without a balanced understanding of the evidence.
One of the main issues to contemplate, and really the main helpful theme in this article, in my opinion, has to do with degree or magnitude: ADHD symptoms exist on a continuum, with everyone in the population having some measurable quantity of attentional capacity, physical restlessness, or impulsivity. These could be considered traits, and each of these traits could be considered useful, positive, and "normal" in some ways, as well as negative or deleterious in others. Medications or other therapies have the capacity to change the degree of symptoms or traits somewhat, for anyone (it is a myth that stimulants improve attention only in those with ADHD). The degree of environmental change required to help an individual escalates rapidly as the degree of symptoms increases. So, there will always be a gray area, of individuals who have more "ADHD symptoms" than the population average, but fewer than those with extreme and highly disabling symptoms. Determining how to help these individuals may be highly influenced by the whims of the local educational or medical culture, combined with the attitudes of the individuals and their families. There may be no absolute, fixed standard possible, to determine exactly when to use a particular form of therapy.
I believe that such decisions should be influenced by the following factors:
1) clear informed consent on the part of individuals and families considering medications or other therapies. This involves having a balanced understanding of evidence, of the risks and benefits of treating and of not treating.
2) thorough assessment with careful attendance to family and psychosocial stresses--never an impulsive prescription of stimulants after a single 5-minute appointment!
3) Follow-up in all cases, with opportunities for talking therapies and behavioural therapy if desired.
4) A reasonable set of nationalized, standardized guidelines for assessment and treatment, to reduce the possibility that a person's geographic location, or the whims of teachers, doctors, journalists, etc. would be strong determinants of whether or not treatment of any kind is offered.
The article attempts to discuss the issue of whether medications are prescribed too often, for treating supposed attention deficit disorder, particularly in male children.
This is a very serious, important question. It warrants careful analysis of the issues, and a balanced evaluation of evidence.
Unfortunately, the article bothered me greatly, because of its bias. Here are some quotes from the article:
Boys: Fixing with a pill is easier than counselling [this was a heading]
There's a desire for the quick fix...the idea that - 'oh, we'll fix this with a pill' - rather than spend a few months in counselling, is pretty appealing. [this was a quote attributed to Gordon Floyd, the CEO of Children's Mental Health Ontario]
What are we drugging? Female teachers who don't understand boys like to run and jump and shout - that's what boys do. [this was a quote attributed to Jon Bradley, an education professor at McGill University]
Prescription rates for ADHD drugs, which like cocaine, are psycho-stimulants...
Mr. Floyd feels counselling stands a better chance of getting to the root of the problem with children, rather than using drugs for years to dull symptoms. Research shows, he says, that talk therapy can be very successful for kids with ADHD.
stimulant drugs may be dangerous for those with underlying heart problems - and those who do not actually have ADHD.
I have often wondered why no real connection has been made between the over-medicalization of our children and the increasing prevalence of illicit drug use in our society. When we give kids the message that they can be 'fixed' by popping a pill, it hardly seems surprising to me that they would later seek to solve their problems by using other available substances. [a quote attributed to Judy McGuire, a "Globe Catalyst"]
The article mentions important issues of concern, including the role of pharmaceutical marketing in changing medication prescription patterns. The diagnosis of ADHD, and the use of medications, appears to vary substantially from one locale to the next. The phenomenon of teachers coercing parents to seek medication treatment for their children is certainly problematic.
But the article did not give a balanced presentation of evidence.
It is more common, in my experience, to encounter young adults who have struggled with ADHD symptoms, without any medication treatment, all their lives. Often times, they, or their parents, have been strongly opposed to the idea of taking medications. Many of these young adults are very intelligent, but often have been unable to sit through the intellectual tasks required to develop their intelligence. Therefore, they have often not been able to achieve the goals which are reasonably available to them. There is really no way around the fact that reading, for example, is necessary to develop one's mind in the modern world; reading requires one to sit still and focus for extended periods of time. A great deal of the discipline required to develop one's intellect requires prolonged focus, often with tasks that are initially perceived to be uninteresting (with discipline, intelligence, and imagination, any so-called "boring" subject can become interesting--but if individuals are unable to focus during the initial "boring" introduction to a subject, this deep interest and engagement may never be found).
Treating ADHD with medication does not increase substance abuse. Rates of substance use in an untreated ADHD population are substantially higher. Here is a reference to a research article demonstrating this: http://www.ncbi.nlm.nih.gov/pubmed/18838643 It is certainly my clinical experience, that subjects with untreated ADHD have much higher rates of substance use, including cigarettes, alcohol, cannabis, and harder drugs. The belief that treating ADHD with medications somehow increases risk for substance abuse, is simply unfounded--the opposite effect has been clearly shown. Exceptions exist, of course, in individual cases where adolescents may be abusing their medication, selling it, etc. Also, in many cases "ADHD" is not the only issue or problem; there may be antisocial behaviour, mood disorders, severe family or psychosocial problems, etc. which also obviously affect risks.
In terms of dangers or risks, it is of course important to examine negative side-effects or toxicity from stimulants. Such an analysis would fairly establish that risks are present, but of low incidence. For example, the risk of stimulants causing heart problems.
But a fair assessment of risk must include consideration of the risks of non-treatment! The obvious risks in an ADHD population are higher risks of accidental injuries, car accidents, sequelae from substance abuse, and reckless interpersonal behaviour. The risk pertains not only to those with untreated ADHD, but also to peers (for example, passengers in a vehicle). Here are a few references evidence about this:
http://www.ncbi.nlm.nih.gov/pubmed/19739058
http://www.ncbi.nlm.nih.gov/pubmed/18815438
http://www.ncbi.nlm.nih.gov/pubmed/10790000
It is also, of course, very important to consider whether counseling or other types of therapy could be helpful for ADHD symptoms. The prevailing evidence shows that there can be small effects with existing therapy styles--this is certainly worth pursuing--but counseling often doesn't work very well. In cases where there are multiple other problems going on (e.g. anxiety, mood, family conflicts, etc.) then of course some type of external counseling support would be preferable to simply obtaining a stimulant prescription. The notion that "a few months of counseling" would make much of a difference for most kids with ADHD symptoms is absurd, and entirely unsupported by any evidence.
The idea of accepting that "that's what boys do," etc. is important to consider. But imagine, as an adult reader, that you are transported to elementary school again. Would it be a pleasant and rewarding situation for you to be in a classroom where the attitude "that's what boys do" prevails? Similar philosophies, in the adult world, have been used to justify various types of antisocial behaviour. The issue is not just about the individuals with so-called ADHD, but also about peers and community. Rambunctiousness need not be pathologized, but a desire for sustained attentiveness need not be pathologized either. Most people with ADHD histories have had serious difficulties not just in classroom settings, but in all spheres of life: home, friendships, community, work, etc. This issue is not just about artificially forcing people into the constraints of a boring, quiet classroom, although admittedly a sedate classroom environment could be a very unhelpful factor for some.
The article seems to suggest that male teachers would be preferable. What does this have to do with anything? Where is the evidence?! Is this claim not an insult to female teachers? And, in my memory, I don't remember male teachers being any better at managing a classroom of rambunctious kids, compared to female teachers. In fact, I can think of counterexamples, in which female teachers could have a gentle, maternal effect on hyperactive kids helping them to enjoy their day, so that their experience of a classroom could be more positive.
I do agree that there are learning or educational styles which could suit some individuals much better. And I agree that having opportunities to be physically active is extremely important--for everyone, not just for "ADHD kids." One of the authors in this article suggests that the decline of opportunities such as "wood shop" (the implication is, that these are mainly for boys) is part of the problem. But, imagine as a wood shop teacher -- where you are in charge of a band saw, a lathe, and a few power nail guns -- that you have a few kids who are easily bored, highly rambunctious, and have difficulty paying attention. Band saw + ADHD! Do you see any problems there?
Some "alternative learning styles" could already begin to produce an unnecessary tier, sending kids with more ADHD symptoms away from a more scholarly focus, towards developing a more physical trade. I don't think there's anything wrong with this per se, unless the child with ADHD symptoms actually wants to develop scholarly pursuits, and/or has an undeveloped talent for the type of scholarship which requires intense focus, and doesn't really want to be "tiered" in this way.
I recognize that this is an important issue, and everyone's point of view needs to be considered to work out the best solutions for health policy and for helping individuals. But this article, in one of Canada's leading newspapers, was disturbingly one-sided, and in my opinion could contribute to many individuals feeling stigmatized or rejecting the possibility of medication therapy without a balanced understanding of the evidence.
One of the main issues to contemplate, and really the main helpful theme in this article, in my opinion, has to do with degree or magnitude: ADHD symptoms exist on a continuum, with everyone in the population having some measurable quantity of attentional capacity, physical restlessness, or impulsivity. These could be considered traits, and each of these traits could be considered useful, positive, and "normal" in some ways, as well as negative or deleterious in others. Medications or other therapies have the capacity to change the degree of symptoms or traits somewhat, for anyone (it is a myth that stimulants improve attention only in those with ADHD). The degree of environmental change required to help an individual escalates rapidly as the degree of symptoms increases. So, there will always be a gray area, of individuals who have more "ADHD symptoms" than the population average, but fewer than those with extreme and highly disabling symptoms. Determining how to help these individuals may be highly influenced by the whims of the local educational or medical culture, combined with the attitudes of the individuals and their families. There may be no absolute, fixed standard possible, to determine exactly when to use a particular form of therapy.
I believe that such decisions should be influenced by the following factors:
1) clear informed consent on the part of individuals and families considering medications or other therapies. This involves having a balanced understanding of evidence, of the risks and benefits of treating and of not treating.
2) thorough assessment with careful attendance to family and psychosocial stresses--never an impulsive prescription of stimulants after a single 5-minute appointment!
3) Follow-up in all cases, with opportunities for talking therapies and behavioural therapy if desired.
4) A reasonable set of nationalized, standardized guidelines for assessment and treatment, to reduce the possibility that a person's geographic location, or the whims of teachers, doctors, journalists, etc. would be strong determinants of whether or not treatment of any kind is offered.
Wednesday, September 29, 2010
Atomoxetine for ADHD
Atomoxetine (Strattera) is one of the pharmacological options for treating ADHD symptoms (attention or concentration problems, hyperactivity, impulsivity) in children and adults. I think it is a good drug, quite safe, quite effective. It is not likely to help with mood or anxiety symptoms. Its effect is probably not quite as robust, for most people, compared to stimulants, but it has the compelling advantage of working continuously throughout the day, instead of wearing off (as the stimulants do) after a few hours. It takes at least 2 weeks of daily dosing for it to work, which differs from the immediate effect of stimulants.
While it has only a 5-hour half-life in the body, it probably works just as well if dosed once-daily compared to twice-daily. Side-effects are usually quite mild, including possible dry mouth and reduced appetite.
It is quite expensive, and is not covered well by medication funding plans in BC.
Here is a brief survey of some of the research literature about atomoxetine that I found interesting:
http://www.ncbi.nlm.nih.gov/pubmed/20665133
This 2010 article demonstrates that once-daily atomoxetine is superior to placebo for treating adult ADHD symptoms, over a 6-month follow-up period. Treated patients typically had about a 30% reduction in their symptom scores. Doses were about 80 mg/day.
http://www.ncbi.nlm.nih.gov/pubmed/18448861
This is an important study, with 4 years of follow-up, treating adult ADHD patients on an open-label basis. The medication was tolerated well, again with ADHD symptom reductions of about 30%. Depression and anxiety symptoms were not affected. I tried unsuccessfully to find a clear statement about average doses used in the study; the dosing regime was similar to other studies, with a maximum of 160 mg/day. From the authors' previous paper on the interim results of this study, the mean dose was about 100 mg/day, the median about 120 mg/day. So these are higher doses than in some of the other studies, which typically had 80 mg/day dosing.
http://www.ncbi.nlm.nih.gov/pubmed/20070786
This was a 6-week open study, showing that adults with "atypical ADHD" showed improvement with atomoxetine treatment, doses averaging about 80 mg/day.
http://www.ncbi.nlm.nih.gov/pubmed/20051220
This is an important 2008 meta-analysis, comparing effect sizes of different therapies for adult ADHD. Short-acting stimulants were best; long-acting stimulants similar (no advantage--if anything, not quite as high an effect size compared to short-acting stimulants); non-stimulants such as atomoxetine significantly helpful, but not quite as large an effect size as stimulants.
http://www.ncbi.nlm.nih.gov/pubmed/17110824This study shows modest but significant improvement in quality-of-life ratings for adult ADHD patients treated with atomoxetine 80 mg/day for 6 weeks.
http://www.ncbi.nlm.nih.gov/pubmed/20642391
This study shows reduction in high-risk behaviours in adolescents treated with atomoxetine over a 40-week period. Looking quickly at the results, I see significant differences between atomoxetine and placebo, but the absolute differences were quite modest in size (typically about a 10% change). Also the study design has a variety of weaknesses.
http://www.ncbi.nlm.nih.gov/pubmed/17474814
This is one of many studies showing that atomoxetine does not help with depressive symptoms. In this case, it was used as an adjunct to an SSRI.
http://www.ncbi.nlm.nih.gov/pubmed/19358788
This study showed no improvement in cognitive function in patients with schizophrenia treated with atomoxetine over 8 weeks. There were no adverse psychiatric effects, however. This is an important area to study, to determine if ADHD treatments such as atomoxetine are psychiatrically safe for those with other major mental illnesses, such as schizophrenia or bipolar disorder.
http://www.ncbi.nlm.nih.gov/pubmed/20679638
This 2010 article from Neurology shows that atomoxetine is not useful for treating depression in Parkinson Disease patients. I find this type of study useful, to look at psychiatric symptoms in medical illnesses. In such situations, the biological impact of the treatment often seems more clear to me, perhaps with fewer confounding psychological factors. The study did find that patients treated with atomoxetine (target dose 80 mg/day) had significantly less daytime sleepiness, and significant improvement in "global cognitive function."
http://www.ncbi.nlm.nih.gov/pubmed/19025777
This similar study shows a possible improvement due to atomoxetine treatment--averaging about 90 mg/day--of executive dysfunction in Parkinson Disease patients. I note also that there was a reduction in other symptom domains, such as apathy and emotional lability; these problems can be difficult to address in those with mood disorders.
http://www.ncbi.nlm.nih.gov/pubmed/17900980
Here's another interesting study, using atomoxetine to treat sleep apnea patients, averaging about 80 mg/day over 4 weeks. The atomoxetine did not help reduce apnea, but it did significantly reduce subjective sleepiness. There are only a couple of fragmentary mentionings of atomoxetine in treating narcolepsy, another disorder of excessive sleepiness; here is one case report: http://www.ncbi.nlm.nih.gov/pubmed/16268387 Excessive sleepiness is another challenging symptom I see a lot of in young adult depression; antidepressants often don't help with the sleepiness, and tolerance tends to develop for stimulants. So atomoxetine may be another useful option.
While it has only a 5-hour half-life in the body, it probably works just as well if dosed once-daily compared to twice-daily. Side-effects are usually quite mild, including possible dry mouth and reduced appetite.
It is quite expensive, and is not covered well by medication funding plans in BC.
Here is a brief survey of some of the research literature about atomoxetine that I found interesting:
http://www.ncbi.nlm.nih.gov/pubmed/20665133
This 2010 article demonstrates that once-daily atomoxetine is superior to placebo for treating adult ADHD symptoms, over a 6-month follow-up period. Treated patients typically had about a 30% reduction in their symptom scores. Doses were about 80 mg/day.
http://www.ncbi.nlm.nih.gov/pubmed/18448861
This is an important study, with 4 years of follow-up, treating adult ADHD patients on an open-label basis. The medication was tolerated well, again with ADHD symptom reductions of about 30%. Depression and anxiety symptoms were not affected. I tried unsuccessfully to find a clear statement about average doses used in the study; the dosing regime was similar to other studies, with a maximum of 160 mg/day. From the authors' previous paper on the interim results of this study, the mean dose was about 100 mg/day, the median about 120 mg/day. So these are higher doses than in some of the other studies, which typically had 80 mg/day dosing.
http://www.ncbi.nlm.nih.gov/pubmed/20070786
This was a 6-week open study, showing that adults with "atypical ADHD" showed improvement with atomoxetine treatment, doses averaging about 80 mg/day.
http://www.ncbi.nlm.nih.gov/pubmed/20051220
This is an important 2008 meta-analysis, comparing effect sizes of different therapies for adult ADHD. Short-acting stimulants were best; long-acting stimulants similar (no advantage--if anything, not quite as high an effect size compared to short-acting stimulants); non-stimulants such as atomoxetine significantly helpful, but not quite as large an effect size as stimulants.
http://www.ncbi.nlm.nih.gov/pubmed/17110824This study shows modest but significant improvement in quality-of-life ratings for adult ADHD patients treated with atomoxetine 80 mg/day for 6 weeks.
http://www.ncbi.nlm.nih.gov/pubmed/20642391
This study shows reduction in high-risk behaviours in adolescents treated with atomoxetine over a 40-week period. Looking quickly at the results, I see significant differences between atomoxetine and placebo, but the absolute differences were quite modest in size (typically about a 10% change). Also the study design has a variety of weaknesses.
http://www.ncbi.nlm.nih.gov/pubmed/17474814
This is one of many studies showing that atomoxetine does not help with depressive symptoms. In this case, it was used as an adjunct to an SSRI.
http://www.ncbi.nlm.nih.gov/pubmed/19358788
This study showed no improvement in cognitive function in patients with schizophrenia treated with atomoxetine over 8 weeks. There were no adverse psychiatric effects, however. This is an important area to study, to determine if ADHD treatments such as atomoxetine are psychiatrically safe for those with other major mental illnesses, such as schizophrenia or bipolar disorder.
http://www.ncbi.nlm.nih.gov/pubmed/20679638
This 2010 article from Neurology shows that atomoxetine is not useful for treating depression in Parkinson Disease patients. I find this type of study useful, to look at psychiatric symptoms in medical illnesses. In such situations, the biological impact of the treatment often seems more clear to me, perhaps with fewer confounding psychological factors. The study did find that patients treated with atomoxetine (target dose 80 mg/day) had significantly less daytime sleepiness, and significant improvement in "global cognitive function."
http://www.ncbi.nlm.nih.gov/pubmed/19025777
This similar study shows a possible improvement due to atomoxetine treatment--averaging about 90 mg/day--of executive dysfunction in Parkinson Disease patients. I note also that there was a reduction in other symptom domains, such as apathy and emotional lability; these problems can be difficult to address in those with mood disorders.
http://www.ncbi.nlm.nih.gov/pubmed/17900980
Here's another interesting study, using atomoxetine to treat sleep apnea patients, averaging about 80 mg/day over 4 weeks. The atomoxetine did not help reduce apnea, but it did significantly reduce subjective sleepiness. There are only a couple of fragmentary mentionings of atomoxetine in treating narcolepsy, another disorder of excessive sleepiness; here is one case report: http://www.ncbi.nlm.nih.gov/pubmed/16268387 Excessive sleepiness is another challenging symptom I see a lot of in young adult depression; antidepressants often don't help with the sleepiness, and tolerance tends to develop for stimulants. So atomoxetine may be another useful option.
Monday, August 17, 2009
ADHD questions
Here are some great questions about ADHD, submitted by a reader:
I don't know the answers to a lot of these, but I am interested to keep trying to learn more. Here's my best response I can come up with for now:
1) First of all, the bottom line of whether something is helpful or not may not be some specific thing, like academic performance. Perhaps "well-being" in a broad, general sense is a more reasonable goal. Yet, things like academic performance are important in life. Perhaps stimulants or other treatments for ADHD are "necessary but not sufficient" to help with ADHD-related academic problems over the longer term. It appears to me from the data that stimulants are actually helpful for academic problems, it's just that the size of the effect is much smaller than what most people would hope for.
2) I wrote a post about zinc supplementation before. Also adequate iron stores are probably important. A generally healthy diet is probably important. I've encountered some people with ADHD who have reduced tolerance for irritation or frustration, and may be particularly bothered or distracted by hunger; yet they may not be organized to have meals prepared regularly through the day. So it can help them manage their ADHD to make sure they always have snacks with them, so that they are never in a hungry state. Other than that, I think there are a lot of nutritional claims out there which have a poor evidence base. The link between sugar intake and hyperactivity is poorly substantiated--I've written a post about that.
Food additives or dyes could play a role in exacerbating ADHD symptoms. Based on this evidence, it makes sense to me to limit food dyes and sodium benzoate in the diet, since such changes do not compromise quality of life in any way, and may lead to improved symptoms. Here are a few references:
http://www.ncbi.nlm.nih.gov/pubmed/17825405
(this is the best of the references: it is from Lancet in 2007)
http://www.ncbi.nlm.nih.gov/pubmed/15613992
http://www.ncbi.nlm.nih.gov/pubmed/15155391
I once attended a presentation on EEG biofeedback. I think it is a promising modality. Harmless to give it a try, but probably expensive. It will be interesting once the technology is available to use EEG biofeedback in front of your own home computer, at low cost.
A few of the self-help books about ADHD are worth reading. There are a lot of practical suggestions about managing symptoms. Some of the books may contain a strongly biased agenda for or against things like stimulants or dietary changes, so you need to be prepared for that possibility.
3)The ADHD label is an artificial, semantic creation, a representation of symptoms or traits which exist on a continuum. Even for those who do not officially satisfy symptom checklist criteria for ADHD, they could benefit substantially from ADHD treatments if there is some component of these symptoms at play neurologically. Many people with apparent disorders of mood, personality, learning, conduct, etc. may have some component of ADHD as well: in some cases ADHD treatments are remarkably helpful for the other problems. So I think careful trials of stimulants could be helpful diagnostically for some people, provided there are no significant contraindications.
4) I've always thought about the ADHD label as just a semantic updating of the previous ADD label. Subtypes of ADHD which are predominantly inattentive rather than hyperactive may differ in terms of comorbidities and prognosis.
5) Hard to say. Many people think of bupropion as a "dopaminergic" drug, whereas bupropion and its relevant metabolites probably act mainly on the norepinephrine system in humans (its dopaminergic activity is more significant in dogs). But perhaps bupropion response could correlate with stimulant response. I haven't seen a good study to show this, nor do I have a case series myself to comment one way or the other based on personal experience.
6) I don't know about that. Comorbidities (e.g. substance use, relationship, or conduct problems) may have accumulated in adults who have not had help during childhood. Yet I have often found it to be the case that the core symptoms of most anything can improve with treatment, at any age.
7) Patients with psychotic disorders (i.e. having a history of hallucinations, delusions, or severely disorganized thinking) often seem to do poorly on stimulants. Patients who are using stimulants primarily to increase energy or motivation often are disappointed with stimulants after a few months, since tolerance develops for effects on energy. Patients with eating disorders could do poorly, since stimulant use may become yet another dysfunctional eating behaviour used to control appetite. And individuals who are trying to use stimulants as part of thrill-seeking behaviour, who are using more than prescribed doses, or who are selling their medication, are worse off for receiving stimulant prescriptions.
1) You write here that long-term use of stimulants has NOT been shown to improve long-term academic outcomes. Why do you think this is, given that symptoms of ADHD improve on medication? (It actually really depresses me to think that individual symptoms can improve, yet no real change takes place...though I know that this might not apply to all patients.
2) What are some effective non-drug treatments for ADHD? I am particularly interested in dietary measures, and also EEG biofeedback.
3) I have read about prescribing psychostimulants as a way of basically diagnosing ADHD...i.e., the diagnosis is based on your response to the medication. I am just wondering how precise this would be, given that stimulants would probably (?) impove most people's concentration, etc. Or is there any role for neuropsychological testing in trying to establish a diagnosis? Is there any way of definitively establishing this kind of diagnosis?
4) I have read that there are many differences between ADD and ADHD, i.e. not just in symptom presentation but in the underlying brain pathology. Is that true? I'm not sure how to phrase it, it seemed like the suggestion was that ADD was more "organic", although maybe that doesn't make sense. Does that have implications for prognosis or treatment strategies?
5) I have read that one red flag that suggests ADD in the context of MDD treatment is a good response to bupropion. If a patient did not have a really good response to bupropion-- or if the response was only partial-- does this usually mean that treatments with psychostimulants like Ritalin, Adderall, etc. will be ineffective (or only partially effective) also?
6) If ADD is not diagnosed/treated until adulthood, is it usually more difficult to treat than if it is diagnosed/ treated in early childhood? Is the response to stimulant treatment just as good? I guess I am wondering if there are certain structural changes that occur in the brain that result from untreated ADD-- kind of like long-term depression and hippocampal atrophy?
7) Is there a certain type of patient who usually does poorly on psychostimulants, or who experiences severe side effects on psychostimulants?
I don't know the answers to a lot of these, but I am interested to keep trying to learn more. Here's my best response I can come up with for now:
1) First of all, the bottom line of whether something is helpful or not may not be some specific thing, like academic performance. Perhaps "well-being" in a broad, general sense is a more reasonable goal. Yet, things like academic performance are important in life. Perhaps stimulants or other treatments for ADHD are "necessary but not sufficient" to help with ADHD-related academic problems over the longer term. It appears to me from the data that stimulants are actually helpful for academic problems, it's just that the size of the effect is much smaller than what most people would hope for.
2) I wrote a post about zinc supplementation before. Also adequate iron stores are probably important. A generally healthy diet is probably important. I've encountered some people with ADHD who have reduced tolerance for irritation or frustration, and may be particularly bothered or distracted by hunger; yet they may not be organized to have meals prepared regularly through the day. So it can help them manage their ADHD to make sure they always have snacks with them, so that they are never in a hungry state. Other than that, I think there are a lot of nutritional claims out there which have a poor evidence base. The link between sugar intake and hyperactivity is poorly substantiated--I've written a post about that.
Food additives or dyes could play a role in exacerbating ADHD symptoms. Based on this evidence, it makes sense to me to limit food dyes and sodium benzoate in the diet, since such changes do not compromise quality of life in any way, and may lead to improved symptoms. Here are a few references:
http://www.ncbi.nlm.nih.gov/pubmed/17825405
(this is the best of the references: it is from Lancet in 2007)
http://www.ncbi.nlm.nih.gov/pubmed/15613992
http://www.ncbi.nlm.nih.gov/pubmed/15155391
I once attended a presentation on EEG biofeedback. I think it is a promising modality. Harmless to give it a try, but probably expensive. It will be interesting once the technology is available to use EEG biofeedback in front of your own home computer, at low cost.
A few of the self-help books about ADHD are worth reading. There are a lot of practical suggestions about managing symptoms. Some of the books may contain a strongly biased agenda for or against things like stimulants or dietary changes, so you need to be prepared for that possibility.
3)The ADHD label is an artificial, semantic creation, a representation of symptoms or traits which exist on a continuum. Even for those who do not officially satisfy symptom checklist criteria for ADHD, they could benefit substantially from ADHD treatments if there is some component of these symptoms at play neurologically. Many people with apparent disorders of mood, personality, learning, conduct, etc. may have some component of ADHD as well: in some cases ADHD treatments are remarkably helpful for the other problems. So I think careful trials of stimulants could be helpful diagnostically for some people, provided there are no significant contraindications.
4) I've always thought about the ADHD label as just a semantic updating of the previous ADD label. Subtypes of ADHD which are predominantly inattentive rather than hyperactive may differ in terms of comorbidities and prognosis.
5) Hard to say. Many people think of bupropion as a "dopaminergic" drug, whereas bupropion and its relevant metabolites probably act mainly on the norepinephrine system in humans (its dopaminergic activity is more significant in dogs). But perhaps bupropion response could correlate with stimulant response. I haven't seen a good study to show this, nor do I have a case series myself to comment one way or the other based on personal experience.
6) I don't know about that. Comorbidities (e.g. substance use, relationship, or conduct problems) may have accumulated in adults who have not had help during childhood. Yet I have often found it to be the case that the core symptoms of most anything can improve with treatment, at any age.
7) Patients with psychotic disorders (i.e. having a history of hallucinations, delusions, or severely disorganized thinking) often seem to do poorly on stimulants. Patients who are using stimulants primarily to increase energy or motivation often are disappointed with stimulants after a few months, since tolerance develops for effects on energy. Patients with eating disorders could do poorly, since stimulant use may become yet another dysfunctional eating behaviour used to control appetite. And individuals who are trying to use stimulants as part of thrill-seeking behaviour, who are using more than prescribed doses, or who are selling their medication, are worse off for receiving stimulant prescriptions.
Wednesday, July 15, 2009
Benefits and Risks of Zinc Supplementation in Eating Disorders, ADHD, and Depression
Zinc supplementation may help treat anorexia nervosa, ADHD, and treatment-resistant depression.
Zinc is a metallic element involved in multiple aspects of human cellular function, metabolism, growth, and immune function. It is required for the function of about 100 human enzymes. The human body contains about 2000-3000 mg of zinc, of which about 2-3 mg are lost daily through kidneys, bowel, and sweat glands. The biologic half-life of zinc in the body is about 9 months, so it can take months or years for changes in dietary habits to substantially change zinc status, unless the intake is very high for short periods.
Red meat is a particularly rich source of zinc. Vegetarians may have a harder time getting an adequate amount from the diet. The prevalence of zinc deficiency may be as high as 40% worldwide.
When referring to zinc dosage, it is best to refer to "elemental zinc". Different types of zinc preparations (e.g. zinc gluconate or zinc sulphate) have different amounts of elemental zinc. For example, 100 mg of zinc gluconate contains about 14 mg of elemental zinc. 110 mg of zinc sulphate contains about 25 mg of elemental zinc.
Here are references to articles written by a Vancouver eating disorders specialist between 1994 and 2006, advising supplementation of 14 mg elemental zinc daily (corresponding to 100 mg zinc gluconate daily) for 2 months in all anorexic patients:
http://www.ncbi.nlm.nih.gov/pubmed/17272939
http://www.ncbi.nlm.nih.gov/pubmed/11930982
http://www.ncbi.nlm.nih.gov/pubmed/8199605
Here's a 1987 article from a pediatrics journal, showing improvement in depression and anxiety following 50 mg/d elemental zinc supplementation in anorexic adolescents:
http://www.ncbi.nlm.nih.gov/pubmed/3312133
In this 1990 open study, anorexic patients were treated with 45-90 mg elemental zinc daily, most of whom had significant improvement in their eating disorder symptoms over 2 years of follow-up.
http://www.ncbi.nlm.nih.gov/pubmed/2291418
Here's a 1992 case report of substantial improvement in severe anorexia following zinc supplementation:
http://www.ncbi.nlm.nih.gov/pubmed/1526438
Zinc depletion may lead to an abnormal sense of taste (hypogeusia or dysgeusia). This sensory abnormality improves with zinc supplementation. Here's a reference:
http://www.ncbi.nlm.nih.gov/pubmed/8835055
Here's a randomized , controlled 2009 Turkish study showing that 10 weeks of 15 mg/day zinc supplementation led to improvement in ADHD symptoms in children. However, a close look at the study shows a bizarre lack of statistical analysis comparing the supplemented group directly with the placebo group. When you look at the data from the article, both groups improved to a modest degree on most measures, with perhaps a little bit more improvement in the zinc group. The analysis here was insufficient, I'm surprised a journal would accept this.
http://www.ncbi.nlm.nih.gov/pubmed/19133873
Here's a 2004 reference to a study showing that 6 weeks of 15 mg elemental zinc daily as an adjunct to stimulant therapy improved ADHD symptoms in children, compared to stimulant therapy plus placebo. In this case, there was a valid statistical analysis:
http://www.ncbi.nlm.nih.gov/pubmed/15070418
Here's a 2009 study showing that zinc supplementation improves the response to antidepressants in treatment-resistant depression. The dose they used was 25 mg elemental zinc daily, over 12 weeks.
http://www.ncbi.nlm.nih.gov/pubmed/19278731
Here's an excellent 2008 review article about zinc deficiency, and about the potential role of zinc supplementation in a wide variety of diseases (e.g. infections ranging from the common cold, to TB, to warts; arthritis; diarrhea; mouth ulcers). The review shows that zinc may have benefit for some of these conditions, but the evidence is a bit inconsistent:
http://www.ncbi.nlm.nih.gov/pubmed/18221847
Here is a warning about zinc toxicity:
http://www.ncbi.nlm.nih.gov/pubmed/12368702 {hematological toxicity from taking 50-300 mg zinc daily for 6-7 months. The toxicity was thought to be due to zinc-induced copper malabsorption leading to sideroblastic anemia}
Here is a nice website from NIH summarizing the role of zinc in the diet, in the body, some of the research about health effects, and about toxicity. It sticks to a recommended daily intake of 10-15 mg elemental zinc for adults, or about 5 mg for young children. It states that the maximum tolerable daily intake levels are about 5-10 mg for young children, 20-30 mg for adolescents, and 40 mg daily for adults:
http://ods.od.nih.gov/FactSheets/Zinc.asp
Here is a reference to another excellent review of zinc requirements, benefits, and risks. It makes more cautious recommendations about zinc supplementation, advising no more than 20 mg/day of zinc intake in adults. In order to prevent copper deficiency, it also advises that that the ratio between zinc intake and copper intake does not exceed 10.
http://www.ncbi.nlm.nih.gov/pubmed/16632171
So, were I to make a recommendation about a zinc supplementation trial, I would advise sticking to amounts under 20 mg (elemental) per day for adults, and to ensure that you are getting 2 mg of copper per day with that.
Zinc is a metallic element involved in multiple aspects of human cellular function, metabolism, growth, and immune function. It is required for the function of about 100 human enzymes. The human body contains about 2000-3000 mg of zinc, of which about 2-3 mg are lost daily through kidneys, bowel, and sweat glands. The biologic half-life of zinc in the body is about 9 months, so it can take months or years for changes in dietary habits to substantially change zinc status, unless the intake is very high for short periods.
Red meat is a particularly rich source of zinc. Vegetarians may have a harder time getting an adequate amount from the diet. The prevalence of zinc deficiency may be as high as 40% worldwide.
When referring to zinc dosage, it is best to refer to "elemental zinc". Different types of zinc preparations (e.g. zinc gluconate or zinc sulphate) have different amounts of elemental zinc. For example, 100 mg of zinc gluconate contains about 14 mg of elemental zinc. 110 mg of zinc sulphate contains about 25 mg of elemental zinc.
Here are references to articles written by a Vancouver eating disorders specialist between 1994 and 2006, advising supplementation of 14 mg elemental zinc daily (corresponding to 100 mg zinc gluconate daily) for 2 months in all anorexic patients:
http://www.ncbi.nlm.nih.gov/pubmed/17272939
http://www.ncbi.nlm.nih.gov/pubmed/11930982
http://www.ncbi.nlm.nih.gov/pubmed/8199605
Here's a 1987 article from a pediatrics journal, showing improvement in depression and anxiety following 50 mg/d elemental zinc supplementation in anorexic adolescents:
http://www.ncbi.nlm.nih.gov/pubmed/3312133
In this 1990 open study, anorexic patients were treated with 45-90 mg elemental zinc daily, most of whom had significant improvement in their eating disorder symptoms over 2 years of follow-up.
http://www.ncbi.nlm.nih.gov/pubmed/2291418
Here's a 1992 case report of substantial improvement in severe anorexia following zinc supplementation:
http://www.ncbi.nlm.nih.gov/pubmed/1526438
Zinc depletion may lead to an abnormal sense of taste (hypogeusia or dysgeusia). This sensory abnormality improves with zinc supplementation. Here's a reference:
http://www.ncbi.nlm.nih.gov/pubmed/8835055
Here's a randomized , controlled 2009 Turkish study showing that 10 weeks of 15 mg/day zinc supplementation led to improvement in ADHD symptoms in children. However, a close look at the study shows a bizarre lack of statistical analysis comparing the supplemented group directly with the placebo group. When you look at the data from the article, both groups improved to a modest degree on most measures, with perhaps a little bit more improvement in the zinc group. The analysis here was insufficient, I'm surprised a journal would accept this.
http://www.ncbi.nlm.nih.gov/pubmed/19133873
Here's a 2004 reference to a study showing that 6 weeks of 15 mg elemental zinc daily as an adjunct to stimulant therapy improved ADHD symptoms in children, compared to stimulant therapy plus placebo. In this case, there was a valid statistical analysis:
http://www.ncbi.nlm.nih.gov/pubmed/15070418
Here's a 2009 study showing that zinc supplementation improves the response to antidepressants in treatment-resistant depression. The dose they used was 25 mg elemental zinc daily, over 12 weeks.
http://www.ncbi.nlm.nih.gov/pubmed/19278731
Here's an excellent 2008 review article about zinc deficiency, and about the potential role of zinc supplementation in a wide variety of diseases (e.g. infections ranging from the common cold, to TB, to warts; arthritis; diarrhea; mouth ulcers). The review shows that zinc may have benefit for some of these conditions, but the evidence is a bit inconsistent:
http://www.ncbi.nlm.nih.gov/pubmed/18221847
Here is a warning about zinc toxicity:
http://www.ncbi.nlm.nih.gov/pubmed/12368702 {hematological toxicity from taking 50-300 mg zinc daily for 6-7 months. The toxicity was thought to be due to zinc-induced copper malabsorption leading to sideroblastic anemia}
Here is a nice website from NIH summarizing the role of zinc in the diet, in the body, some of the research about health effects, and about toxicity. It sticks to a recommended daily intake of 10-15 mg elemental zinc for adults, or about 5 mg for young children. It states that the maximum tolerable daily intake levels are about 5-10 mg for young children, 20-30 mg for adolescents, and 40 mg daily for adults:
http://ods.od.nih.gov/FactSheets/Zinc.asp
Here is a reference to another excellent review of zinc requirements, benefits, and risks. It makes more cautious recommendations about zinc supplementation, advising no more than 20 mg/day of zinc intake in adults. In order to prevent copper deficiency, it also advises that that the ratio between zinc intake and copper intake does not exceed 10.
http://www.ncbi.nlm.nih.gov/pubmed/16632171
So, were I to make a recommendation about a zinc supplementation trial, I would advise sticking to amounts under 20 mg (elemental) per day for adults, and to ensure that you are getting 2 mg of copper per day with that.
Thursday, May 7, 2009
Long-term stimulants & ADHD
The long-term use of stimulants such as methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and mixed amphetamine salts (Adderall), in the treatment of attention or behaviour problems in children and adults, has been a controversial issue.
Symptoms of so-called ADHD include inability to sustain attention while doing academic, social, domestic, or work activities; restlessness, and inability to sit quietly or wait patiently. Of course, everyone has difficulties in these domains at times. The diagnosis of ADHD is intended to apply to individuals whose symptoms are so severe in these areas that it causes serious, ongoing problems functioning socially, academically, and with other life tasks. Those with an ADHD diagnosis are much more likely to drop out of school, to be unable to maintain jobs, to have difficulty maintaining friendships, and to have conduct problems ultimately leading to problems with the law, etc.
It is abundantly clear, from careful research, that stimulants improve symptoms of ADHD, and associated problems with social behaviour and disordered conduct.
I do not see good evidence that stimulants adversely affect personality traits or sense of self. Rather, in many cases, the experience of having severe untreated ADHD symptoms adversely affects personality traits and sense of self.
I will add to this post later, to discuss potential adverse effects from stimulant therapy. But stimulants are generally well-tolerated, with a low risk of serious adverse effects for most people.
Existing psychosocial treatments can help ADHD symptoms as well, but they do not work as well as stimulants, and--surprisingly--combining psychosocial treatments with stimulant therapy does not work much better than stimulants alone, except possibly for some individual cases. Here is some evidence, from a 2008 meta-analysis, for this finding:
http://www.ncbi.nlm.nih.gov/pubmed/18068284
Here are a few other important studies pertaining to long-term stimulant use:
This 5 year prospective study shows that stimulant therapy substantially reduces the rate of smoking and substance use disorders in adolescents with ADHD:
http://www.ncbi.nlm.nih.gov/pubmed/18838643
About 20% of ADHD adolescents treated with stimulants over 5 years developed a substance use disorder, compared to 55% of ADHD adolescents not treated with stimulants.
Stimulant-treated adolescents also had much lower rates of smoking. This is a very strong and compelling study, showing profound reductions in addictive disorders as a result of long-term stimulant treatment.
This 2008 study looked at a group of 169 children with ADHD, and followed up on them 9 years later:
http://www.ncbi.nlm.nih.gov/pubmed/18928410
The children who had taken stimulant treatment for their ADHD fared better than those with ADHD who had not taken stimulants, in terms of academic performance (as measured in several different ways). Neither ADHD group performed as well as a comparison group without ADHD.
This 2007 study from the Journal of Developmental and Behavioral Pediatrics is particularly strong, in that it looks at an entire birth cohort (all 5718 children born in Rochester between 1976-1982, of whom 370 with ADHD were identified):
http://www.ncbi.nlm.nih.gov/pubmed/17700079
It looked at long-term outcomes, over an average of 18 years. The study shows reduced absenteeism, reduced likelihood of being held back a grade, and slightly higher reading test scores, for ADHD children receiving long-term stimulant therapy.
Reading scores were particularly higher in the children who had received high doses of stimulants for longer periods of time.
The stimulant group did not differ from the non-stimulant group with respect to sociodemographic variables or duration of follow-up. The study was retrospective and was not randomized, yet it remains a very strong piece of evidence about long-term effects of stimulant treatment for ADHD.
I think these findings emphasize a number of things:
1) stimulants work very well for ADHD symptoms
2) stimulants unfortunately only have a slight effect on long-term academic outcomes
3) existing psychosocial treatments work modestly well on their own, but for most people do not add to the benefits of stimulants. The psychosocial treatments did not improve long-term academic outcomes. The duration of psychosocial treatment did not correlate with better improvement in symptoms, so the weakness of existing psychosocial treatments is not likely due to inadequate length of treatment.
4) long-term stimulant therapy may substantially reduce the risk of ADHD kids getting into alcohol use, substance use, or smoking problems. This finding is strong evidence against the idea that stimulant use increases the risk for subsequent addictive disorders.
I do think we need to keep working on better psychosocial treatments. I suspect that intensive, long-term, individualized treatment, with a style which suits the personality and strengths of each person, will be most effective. And I suspect that such treatments would need to be combined with positive, supportive milieux at home, school, work, and in peer relationships.
I will add to this post, or write a sequel post, to discuss other treatments for ADHD, such as atomoxetine, antidepressants, EEG biofeedback, dietary modification, and some newer psychosocial treatment ideas.
Symptoms of so-called ADHD include inability to sustain attention while doing academic, social, domestic, or work activities; restlessness, and inability to sit quietly or wait patiently. Of course, everyone has difficulties in these domains at times. The diagnosis of ADHD is intended to apply to individuals whose symptoms are so severe in these areas that it causes serious, ongoing problems functioning socially, academically, and with other life tasks. Those with an ADHD diagnosis are much more likely to drop out of school, to be unable to maintain jobs, to have difficulty maintaining friendships, and to have conduct problems ultimately leading to problems with the law, etc.
It is abundantly clear, from careful research, that stimulants improve symptoms of ADHD, and associated problems with social behaviour and disordered conduct.
I do not see good evidence that stimulants adversely affect personality traits or sense of self. Rather, in many cases, the experience of having severe untreated ADHD symptoms adversely affects personality traits and sense of self.
I will add to this post later, to discuss potential adverse effects from stimulant therapy. But stimulants are generally well-tolerated, with a low risk of serious adverse effects for most people.
Existing psychosocial treatments can help ADHD symptoms as well, but they do not work as well as stimulants, and--surprisingly--combining psychosocial treatments with stimulant therapy does not work much better than stimulants alone, except possibly for some individual cases. Here is some evidence, from a 2008 meta-analysis, for this finding:
http://www.ncbi.nlm.nih.gov/pubmed/18068284
Here are a few other important studies pertaining to long-term stimulant use:
This 5 year prospective study shows that stimulant therapy substantially reduces the rate of smoking and substance use disorders in adolescents with ADHD:
http://www.ncbi.nlm.nih.gov/pubmed/18838643
About 20% of ADHD adolescents treated with stimulants over 5 years developed a substance use disorder, compared to 55% of ADHD adolescents not treated with stimulants.
Stimulant-treated adolescents also had much lower rates of smoking. This is a very strong and compelling study, showing profound reductions in addictive disorders as a result of long-term stimulant treatment.
This 2008 study looked at a group of 169 children with ADHD, and followed up on them 9 years later:
http://www.ncbi.nlm.nih.gov/pubmed/18928410
The children who had taken stimulant treatment for their ADHD fared better than those with ADHD who had not taken stimulants, in terms of academic performance (as measured in several different ways). Neither ADHD group performed as well as a comparison group without ADHD.
This 2007 study from the Journal of Developmental and Behavioral Pediatrics is particularly strong, in that it looks at an entire birth cohort (all 5718 children born in Rochester between 1976-1982, of whom 370 with ADHD were identified):
http://www.ncbi.nlm.nih.gov/pubmed/17700079
It looked at long-term outcomes, over an average of 18 years. The study shows reduced absenteeism, reduced likelihood of being held back a grade, and slightly higher reading test scores, for ADHD children receiving long-term stimulant therapy.
Reading scores were particularly higher in the children who had received high doses of stimulants for longer periods of time.
The stimulant group did not differ from the non-stimulant group with respect to sociodemographic variables or duration of follow-up. The study was retrospective and was not randomized, yet it remains a very strong piece of evidence about long-term effects of stimulant treatment for ADHD.
I think these findings emphasize a number of things:
1) stimulants work very well for ADHD symptoms
2) stimulants unfortunately only have a slight effect on long-term academic outcomes
3) existing psychosocial treatments work modestly well on their own, but for most people do not add to the benefits of stimulants. The psychosocial treatments did not improve long-term academic outcomes. The duration of psychosocial treatment did not correlate with better improvement in symptoms, so the weakness of existing psychosocial treatments is not likely due to inadequate length of treatment.
4) long-term stimulant therapy may substantially reduce the risk of ADHD kids getting into alcohol use, substance use, or smoking problems. This finding is strong evidence against the idea that stimulant use increases the risk for subsequent addictive disorders.
I do think we need to keep working on better psychosocial treatments. I suspect that intensive, long-term, individualized treatment, with a style which suits the personality and strengths of each person, will be most effective. And I suspect that such treatments would need to be combined with positive, supportive milieux at home, school, work, and in peer relationships.
I will add to this post, or write a sequel post, to discuss other treatments for ADHD, such as atomoxetine, antidepressants, EEG biofeedback, dietary modification, and some newer psychosocial treatment ideas.
Monday, October 27, 2008
Sugar
Many people believe that sugar (sucrose) intake causes behavioural problems. The two most common specific beliefs are that eating sugar causes worsened hyperactivity; or that eating sugar causes a rush of energy, followed by a plunge into fatigue as the sugar level "crashes".
In fact there have been a lot of very good studies looking at this, and the evidence is quite clear that sugar does not cause hyperactivity. There is an association between high sugar intake and antisocial behaviour, but the relationship is probably not causal. It is much more plausible that those with more antisocial behaviour in the first place happen to choose to consume more sugar.
In some of the prospective, randomized studies, in fact, individuals consuming sugar (instead of a placebo) did better, particularly in terms of learning tasks.
The evidence is also very clear that so-called "reactive hypoglycemia" is very rare, even in people who insist that they have it. However, there may be some individuals who become more irritable as their blood glucose level drops, even if the drop is not down to clinically hypoglycemic levels.
There is evidence that some individuals may respond adversely, in terms of their behaviour, to certain foods, but actually sugar is not a common such food, according to well-controlled studies.
I do affirm that moderating sugar intake, and also eating meals with a lower glycemic index, is part of overall good long-term health.
But most of the claims about sugar influencing behaviour adversely are part of a myth, not supported by clear evidence.
For an excellent review of the evidence on this matter, see this article by David Benton (May 2008):
http://www.informaworld.com/smpp/content~db=all?content=10.1080/10408390701407316
In fact there have been a lot of very good studies looking at this, and the evidence is quite clear that sugar does not cause hyperactivity. There is an association between high sugar intake and antisocial behaviour, but the relationship is probably not causal. It is much more plausible that those with more antisocial behaviour in the first place happen to choose to consume more sugar.
In some of the prospective, randomized studies, in fact, individuals consuming sugar (instead of a placebo) did better, particularly in terms of learning tasks.
The evidence is also very clear that so-called "reactive hypoglycemia" is very rare, even in people who insist that they have it. However, there may be some individuals who become more irritable as their blood glucose level drops, even if the drop is not down to clinically hypoglycemic levels.
There is evidence that some individuals may respond adversely, in terms of their behaviour, to certain foods, but actually sugar is not a common such food, according to well-controlled studies.
I do affirm that moderating sugar intake, and also eating meals with a lower glycemic index, is part of overall good long-term health.
But most of the claims about sugar influencing behaviour adversely are part of a myth, not supported by clear evidence.
For an excellent review of the evidence on this matter, see this article by David Benton (May 2008):
http://www.informaworld.com/smpp/content~db=all?content=10.1080/10408390701407316
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