Stimulant drugs like methylphenidate and dextro-amphetamine for ADHD are among the most well-established therapeutic drugs in all of psychiatry (see for example my article, 40 years of methylphenidate treatment of ADHD, J of Attention Disorders, 2002, Vol. 6, Supplement 1). One reason for this general acceptance is a large number of well-controlled trials repeated by many different investigators over the years. But more importantly, frequent clinical use over many years supports the conclusion of the efficacy and safety of these drugs. Though not without some controversy and certain drawbacks, on the whole it is safe to say that most reputable scientists and clinicians find these stimulants to be of substantial value in treatment of an otherwise very refractory disorder.
But as the success of these drugs has encouraged pharmaceutical companies to seek even more effective drugs, or to market drugs that provide an alternative for those patients who prove refractory to the stimulants, many novel chemical agents are appearing in new drug trials. In addition, potent new anti-psychotic drugs are being touted as safe and effective. Are the drug trials for these newer drugs adequate, or are there serious loopholes in the methodology that allow ineffective or dangerous drugs to be approved?
Here's what often happens in the development of a new psychoactive drug for ADHD. Someone has an idea that a particular molecule, perhaps from a failed trial of some other condition like depression or Alzheimer's or schizophrenia might work with ADHD. An "open label" trial by a proponent is found to produce some favorable response in a few patients by a welll-known clinician treating ADHD, suggesting to the pharmaceutical company that it is worth doing a more carefully controlled trial. (Of course it is financially profitable for the clinician to find positive results because further trials will potentially bring in big bucks, and the pharma company tends to trust the clinical judgments of well-known clinician experts in the field.)
Sometimes a well-meaning investigator finds that although the main experiment failed to confirm the efficacy of the drug, a few patients showed a dramatic improvement, warranting a further look. One of my favorite maxims is that "looking for a subgroup in an experiment is a sure sign of a failed experiment." Pursuing a small lead in a failed experiment is like betting on a nag that put up a good effort but lost.
But pharmaceutical companies have experts in drug trial methodology who also know that they must conform to the standards set by the FDA, and eventually must fund large trials that employ a standard double-blind design, using approved measures. Typically, this means that patients are randomly assigned to a treatment group and a placebo control group, and assessed with a symptom list of some sort representing the current diagnostic standards, such as a DSM-4 checklist. After getting measures before treatment starts ("baseline") subsequent checklists or scales are filled out based upon an interview with the patients (or in the case of children, their parents and/or teachers).
So a parent might respond to questions about hyperactivity, inattention, defiance, or social behavior for example; and the investigator will then fill out his or her own scale, or perhaps a "global" judgment of overall improvement or change. Sounds reasonable. But wait, there are some issues here!
What if the parent or teacher or the patient is able to "peek through the double blind," that is to guess which treatment they are receiving? Not that they would consciously cheat, but because it is well-known that the first thing a patient or parent wants to do is please the doctor, or to do what they think the investigator or doctor wants to find. This is called the "demand character" of an experiment, which every experimenter learns to expect and tries to avoid.
But how can the patient or parent peek through and know which treatment is being used? Easy. Every drug produces some subjective effect, perhaps a side effect like stomach pain or nausea, or a racing heart, or a thousand other subtle or obvious bodily changes. When the patient experiences one of these effects, they will often respond in the way their brain expects. This is called the "cognitive potentiation of a bodily feeling." Let me illustrate from a very early experiment carried out by Stanley Schacter.
Subjects in a drug experiment were told they would receive a drug that would cause some changes in their mood. One group was told that the drug (epinephrine) would make them feel euphoric, and another group was told that the drug would cause them to feel depressed. Now epinephrine is a stimulant that typically will increase heart rate, but the behavioral effect that occurred in this experiment depended upon which expectation the subjects had about the drug, and they acted accordingly. Even though epinephrine produces a number of peripheral signs of stimulation, patients interpreted those signs as if they got a depressant, not a stimulant.
Another favorite experiment was with medical students who were asked to drink coffee and then have measures of heart rate, respiration, and skin temperature taken. One group saw the experimenter brew the coffee from a brand coffee jar (Folger's as I recall), and the other group saw that the jar was labeled as decaf. In fact, both groups got only decaf. But the supposedly "loaded" coffee group had increases in heart rate, respiration and finger temperature, while the "decaf" group showed no changes. This study illustrates how the subjects' expectations can manipulate their own bodily responses.
Returning to ADHD, we now see that when an investigator uses the report by a patient, a parent, or a teacher, there is the possibility that "improvement" will simply be the desire to please the investigator as informed by their own knowledge of the "active" treatment condition. Thus, the double-blind is leaking all over the place.
But there is an even more deadly threat to the integrity of these experiments. In many cases it is the most senior member of the investigating team, the accredited specialist or doctor, who records the signs of improvement. This is so because there is always the possibility of significant "adverse events" or AEs caused by the drug, and the senior investigator must be vigilant in detecting and reporting these AEs for the safety of the patient as well as for eventual calculation of the risk and benefit of the drug. So in these trials, the dose of the drug will usually be adjusted to get a good response without undue side effects or AEs. But if the doc is knowledgeable about the side effects, isn't he or she also then apprised of which drug the patient is receiving? Obviously. Well then, even the honest doc might unconsciously want to please their sponsor by finding positive results. And of course if it is an openly greedy doc, what would you expect?
Funny, though, when I raise these objections in pharmaceutical meetings about the drug results, nobody seems to care. The drug companies persist in believing that the investigator is objectively recording their observations as far as improvement is concerned, while nevertheless being apprised of the side effects. And the investigators themselves never question their own objectivity despite the clear knowledge of who is being treated with what.
These problems might not matter much with the proven stimulants because the efficacy is often so dramatic; but when a more subtle drug effect occurs, who knows what might happen? In fact, I know of more than one such drug that got approved but began to falter after a longer period of clinical use showed the true lack of efficacy. The old maxim in psychopharmacology is worth remembering: "Use a new drug quickly, while it still works."
This is not to allege conscious impropriety. Investigators may truly believe they are objective and drug companies are simply following the models set up as appropriate by the FDA. But there are some simple solutions to these dilemmas, but not without cost. One solution is to use an "active placebo," where a dummy drug is used as a control, producing some bodily effects without much behavioral effect. But this solution has its own problems and is seldom used.
Another solution, and the most logical one, is to have one well-trained physician recording and judging the side effects (and therefore changing the dosages during the adjustment phases of the experiment), and a different experimenter/physician recording the improvement. This requires careful scripting of the protocol for inquiring about improvement, and careful shielding of one investigator from the other colleague.
I often wonder how much subterranean motives influence the investigator, who stands to profit from a successful trial, and the drug company which seeks FDA approval and a rich reward for their investiment. In general I choose to believe in the honesty and integrity of both the docs and the companies. But I also believe in the deeper effects of "demand qualities of the experiment," and the power of placebo when potentiated by cognitions, therefore that we must employ the most rigorous protections possible in our experiments on behalf of our trusting and troubled patients.
Tuesday, May 26, 2009
Monday, November 24, 2008
Neurofeedback and ADHD: Save your money!
At one point many of us in ADHD World were very interested in electrical activity in the brain. There were dramatic demonstrations around, such as using electrical output of the brain to control a toy train set. There seemed to be a nice set of brain rhythms in separate categories, going from very slow during sleep phases, to very fast during active thinking and cognition.
Measurement was easy. There seemed to be correlations with mental state, as when the large-amplitude waves between 8 and 12 Hz were accompanied by a state of alert relaxation. I became entranced with the idea that one could use those rhythms to alter mental states. I was convinced that all the benefits of meditation could be created by finding the key electrical signatures for meditation, and using those outputs (easily obtained with simple amplifiers and filters), to achieve the Nirvana-like states attributed to meditation.
In my naive and excited optimism I carried a portable EEG machine to Nepal to measure the brain activity of highly practiced monks during meditation, (After all, attaching electrodes to the scalp of bald monks beats the messy efforts with long-haired practitioners at home.)
The kindly head of the Buddhist order in Nepal, the Bikku Sumangala, made arrangements for me to obtain my data. He laughed at the idea that I would "find" attention through those little wires attached to the head. Instead he said he could show me how to do it very easily without the wires. So he gave me instruction in meditation of the "mindfulness" variety, and I abandoned my silly escapade in favor of studying the readily observable processes in my own mind. As he said, "Simple, but not easy!)
However, when I returned to my laboratory, then at the University of Pittsburgh, I continued to use biofeedback with a variety of patients, particularly those with anxiety and various kinds of muscle pain and headache. I gradually learned that the biofeedback instruments could mostly be replaced by simple relaxation instructions and practice.
I had one instructive patient, a middle-aged woman who suffered from recurrent tension headaches, whom I treated with simple relaxation patter, with great success in the lab, where I could see in the sessions how well her frontalis muscles relaxed when I gave her the verbal relaxing patter. I gave her a tape with my voice giving the relaxation instructions, to play as homework. After a couple of weeks she returned saying that this cognitive approach was working very well; headaches were gone! I commended her for doing her homework and listening to the tape, whereupon she said, "Oh I found I didn't have to actually listen to it; I just carry the tape around in my purse and it works just as well as listening." Well, we might call this "cue-induced relaxation" in which a visible object has become a cue for the verbal material previously learned. But even this bit of technology can be supplanted rather easily.
But the fact that the EEG machine could readily differentiate the different levels of electrical activity available at the scalp, and that the different rhythms could be used to trigger events that could reward or increase some rhythms and decrease others, as for example, increasing alpha or beta rhythms while decreasing Theta or Delta rhythms, led many others to the idea that it might be possible to permanently change the resting states of the brain, or to give the practitioner a tool for correcting undesired mental states (like the sluggish or sleepy brain which is often associated with conduct problems).
Thus was born a rapidly expanding movement called Neurofeedback, where practitioners charge substantial fees over many sessions to alter the brain states and to give some self-control over those brain states to the clients.
In ADHD and conduct disorders, it was in fact well-known that they tended to have more slowing of occipital waves on average, and less of the faster rhythms associated with higher order mentation. By sounding a simple tone or giving some visual feedback when the desired rhythms occur, it turns out to be quite true that for most people they will be able to alter their own brain rhythms!
But now comes the crucial question: How well does that self-alteration of brain wave control translate into improved behavior? Do the symptoms of ADHD or conduct disturbances, --or anxiety or whatever--stay improved over time? How does one find out?
The obvious answer is, you ask the client. But here is a problem, doesn't the mere expensive exercise itself create a large placebo effect? Well, yes. The fancier the machine, the more convincing the therapist, the more that plain old placebo effect takes over.
Okay then, it seems obvious that practitioners can simply do some controlled studies in which one group gets real feedback, one group gets false feedback, and perhaps one group gets no feedback. Sounds easy, but in practice there are significant problems. How does one give false feedback that seems real and does not discourage the client because nothing is happening? Remember that the client begins to shape their EEG when the feedback tells them what to increase or disregard. False feedback would be discouraging since no changes in brain output would be there to reward changing in the right direction.
Another problem is that clients might well be on some medications to improve their behavior. Many of the so-called supported trials reported in the literature ignore the fact that many of the biofeedback patients were also getting treated with a stimulant drug or other drug. If so, this could likely confound the results or wash out any changes due to the feedback. Sure, one could pick unmedicated patients, though this creates a problem in how representative the ADHD sample would be.
Having clients evaluate their treatment has a serious flaw as well. The client is not "blind" to the treatment conditions, and typically wants to follow the doctor's expectations and improve according to the prescribed outcome. This is called the "demand characteristics" of the experiment, and is often the main thing causing the treatment to "work." So to counter this problem one can have independent evaluators: not the doctor giving the treatment and aware of the side effects, but truly independent observers, perhaps teachers or parents, who can evaluate the behavioral changes without knowing which treatment was being given.
Surprisingly, there are no controlled evaluations of Neurofeedback that deal with the various threats to experimental validity. The main clue here is that most Neurofeedback specialists are "true believers" who don't need evidence to bolster their belief in the programs. They charge a lot of money and show little interest in the scientific support for treatment effects for tracking the followup status of their clients. The key is that the practitioners do not publish controlled outcome studies in reputable peer-reviewed scientific journals. Until they do, clients are advised to ignore the blandishments of the seductive machines and pretty blinking lights.
But they may want to look into mindfulness meditation as a potential avenue for the simple, but not easy approach. In future posts we will look at the evidence for the value of mindfulness meditation or other attention-training approaches.
Measurement was easy. There seemed to be correlations with mental state, as when the large-amplitude waves between 8 and 12 Hz were accompanied by a state of alert relaxation. I became entranced with the idea that one could use those rhythms to alter mental states. I was convinced that all the benefits of meditation could be created by finding the key electrical signatures for meditation, and using those outputs (easily obtained with simple amplifiers and filters), to achieve the Nirvana-like states attributed to meditation.
In my naive and excited optimism I carried a portable EEG machine to Nepal to measure the brain activity of highly practiced monks during meditation, (After all, attaching electrodes to the scalp of bald monks beats the messy efforts with long-haired practitioners at home.)
The kindly head of the Buddhist order in Nepal, the Bikku Sumangala, made arrangements for me to obtain my data. He laughed at the idea that I would "find" attention through those little wires attached to the head. Instead he said he could show me how to do it very easily without the wires. So he gave me instruction in meditation of the "mindfulness" variety, and I abandoned my silly escapade in favor of studying the readily observable processes in my own mind. As he said, "Simple, but not easy!)
However, when I returned to my laboratory, then at the University of Pittsburgh, I continued to use biofeedback with a variety of patients, particularly those with anxiety and various kinds of muscle pain and headache. I gradually learned that the biofeedback instruments could mostly be replaced by simple relaxation instructions and practice.
I had one instructive patient, a middle-aged woman who suffered from recurrent tension headaches, whom I treated with simple relaxation patter, with great success in the lab, where I could see in the sessions how well her frontalis muscles relaxed when I gave her the verbal relaxing patter. I gave her a tape with my voice giving the relaxation instructions, to play as homework. After a couple of weeks she returned saying that this cognitive approach was working very well; headaches were gone! I commended her for doing her homework and listening to the tape, whereupon she said, "Oh I found I didn't have to actually listen to it; I just carry the tape around in my purse and it works just as well as listening." Well, we might call this "cue-induced relaxation" in which a visible object has become a cue for the verbal material previously learned. But even this bit of technology can be supplanted rather easily.
But the fact that the EEG machine could readily differentiate the different levels of electrical activity available at the scalp, and that the different rhythms could be used to trigger events that could reward or increase some rhythms and decrease others, as for example, increasing alpha or beta rhythms while decreasing Theta or Delta rhythms, led many others to the idea that it might be possible to permanently change the resting states of the brain, or to give the practitioner a tool for correcting undesired mental states (like the sluggish or sleepy brain which is often associated with conduct problems).
Thus was born a rapidly expanding movement called Neurofeedback, where practitioners charge substantial fees over many sessions to alter the brain states and to give some self-control over those brain states to the clients.
In ADHD and conduct disorders, it was in fact well-known that they tended to have more slowing of occipital waves on average, and less of the faster rhythms associated with higher order mentation. By sounding a simple tone or giving some visual feedback when the desired rhythms occur, it turns out to be quite true that for most people they will be able to alter their own brain rhythms!
But now comes the crucial question: How well does that self-alteration of brain wave control translate into improved behavior? Do the symptoms of ADHD or conduct disturbances, --or anxiety or whatever--stay improved over time? How does one find out?
The obvious answer is, you ask the client. But here is a problem, doesn't the mere expensive exercise itself create a large placebo effect? Well, yes. The fancier the machine, the more convincing the therapist, the more that plain old placebo effect takes over.
Okay then, it seems obvious that practitioners can simply do some controlled studies in which one group gets real feedback, one group gets false feedback, and perhaps one group gets no feedback. Sounds easy, but in practice there are significant problems. How does one give false feedback that seems real and does not discourage the client because nothing is happening? Remember that the client begins to shape their EEG when the feedback tells them what to increase or disregard. False feedback would be discouraging since no changes in brain output would be there to reward changing in the right direction.
Another problem is that clients might well be on some medications to improve their behavior. Many of the so-called supported trials reported in the literature ignore the fact that many of the biofeedback patients were also getting treated with a stimulant drug or other drug. If so, this could likely confound the results or wash out any changes due to the feedback. Sure, one could pick unmedicated patients, though this creates a problem in how representative the ADHD sample would be.
Having clients evaluate their treatment has a serious flaw as well. The client is not "blind" to the treatment conditions, and typically wants to follow the doctor's expectations and improve according to the prescribed outcome. This is called the "demand characteristics" of the experiment, and is often the main thing causing the treatment to "work." So to counter this problem one can have independent evaluators: not the doctor giving the treatment and aware of the side effects, but truly independent observers, perhaps teachers or parents, who can evaluate the behavioral changes without knowing which treatment was being given.
Surprisingly, there are no controlled evaluations of Neurofeedback that deal with the various threats to experimental validity. The main clue here is that most Neurofeedback specialists are "true believers" who don't need evidence to bolster their belief in the programs. They charge a lot of money and show little interest in the scientific support for treatment effects for tracking the followup status of their clients. The key is that the practitioners do not publish controlled outcome studies in reputable peer-reviewed scientific journals. Until they do, clients are advised to ignore the blandishments of the seductive machines and pretty blinking lights.
But they may want to look into mindfulness meditation as a potential avenue for the simple, but not easy approach. In future posts we will look at the evidence for the value of mindfulness meditation or other attention-training approaches.
Monday, November 17, 2008
Executive Function and ADHD
"Executive Functions" are brain processes that control other brain processes. Specific tasks that involve sensory functions, movement, perception, preparation for action, etc. are organized, regulated, and controlled by higher-order circuits in the brain.
We liken executive functions to those of an executive or CEO in a big corporation, or to the general at the rear of the battlefield or the conductor of a symphony. He or she does not personally sell, do the accounting, collect receipts, schedule the airline flights, do the advertising for the company, or go out on patrol or dig the trenches. (Perhaps the occasional conductor such as Leonard Bernstein will play the piano while also conducting; some CEO's or conductors are genius enough to multi-task at times.)
But the CEO makes the major decisions and policy programs for the company, does the strategic planning, and selects the managers who design and carry out specific tactics. The CEO initiates programs, plans the strategies, monitors the progress, and evaluates the outcomes. The CEO adapts and changes the program as new circumstances require.
But the CEO is vulnerable. If the secretary is absent for a day, scheduling is hampered, monitoring is suspended, and there may be a temporary loss of control. The CEO is effectively brain-dead as far as the momentary functions of the corporation are concerned. Of course, a good hierarchy always includes trustworthy backups, 3-star generals, or first violins who can take over in an emergency. So too in the brain; not all executive functions are vested in a single overall Director, and it is the redundancy of the developed brain that carries on under temporary emergency conditions.
For example, fMRI brain imaging shows that when one of the major executive functions carried out in the anterior cingulate (an area of the brain involved in regulating attention) is impaired in an ADHD adult, the functions are apparently transferred to lateral areas of the brain not typically designed for those functions, perhaps with some loss of proficiency but enough to allow continued overall processing to continue.
So executive functions are powerful functions, mainly located in the newer areas of the brain (the frontal lobes, both orbital and lateral areas) that include such processes as working memory, inhibition of motor response, and selective attention). Many observers of ADHD have proposed that these Executive Functions are the primary processes that define ADHD. They argue that the ability to plan, organize, initiate and complete tasks, monitor the results of actions, inhibit impulse, regulate time requirements such as being on time or estimating the time to do things, and a host of other functions are the hallmark of ADHD; in fact constitute the primary deficits of ADHD.
But does evidence really support this appealing idea? There are several reasons why I think not.
We liken executive functions to those of an executive or CEO in a big corporation, or to the general at the rear of the battlefield or the conductor of a symphony. He or she does not personally sell, do the accounting, collect receipts, schedule the airline flights, do the advertising for the company, or go out on patrol or dig the trenches. (Perhaps the occasional conductor such as Leonard Bernstein will play the piano while also conducting; some CEO's or conductors are genius enough to multi-task at times.)
But the CEO makes the major decisions and policy programs for the company, does the strategic planning, and selects the managers who design and carry out specific tactics. The CEO initiates programs, plans the strategies, monitors the progress, and evaluates the outcomes. The CEO adapts and changes the program as new circumstances require.
But the CEO is vulnerable. If the secretary is absent for a day, scheduling is hampered, monitoring is suspended, and there may be a temporary loss of control. The CEO is effectively brain-dead as far as the momentary functions of the corporation are concerned. Of course, a good hierarchy always includes trustworthy backups, 3-star generals, or first violins who can take over in an emergency. So too in the brain; not all executive functions are vested in a single overall Director, and it is the redundancy of the developed brain that carries on under temporary emergency conditions.
For example, fMRI brain imaging shows that when one of the major executive functions carried out in the anterior cingulate (an area of the brain involved in regulating attention) is impaired in an ADHD adult, the functions are apparently transferred to lateral areas of the brain not typically designed for those functions, perhaps with some loss of proficiency but enough to allow continued overall processing to continue.
So executive functions are powerful functions, mainly located in the newer areas of the brain (the frontal lobes, both orbital and lateral areas) that include such processes as working memory, inhibition of motor response, and selective attention). Many observers of ADHD have proposed that these Executive Functions are the primary processes that define ADHD. They argue that the ability to plan, organize, initiate and complete tasks, monitor the results of actions, inhibit impulse, regulate time requirements such as being on time or estimating the time to do things, and a host of other functions are the hallmark of ADHD; in fact constitute the primary deficits of ADHD.
But does evidence really support this appealing idea? There are several reasons why I think not.
- First of all. there is the problem that the very definition of what constitutes executive functions varies from one authority to another; there is no standard or accepted definition.
- When parents or teachers fill out checklists or ratings of executive functions, there appears to be agreement with standard definitions of ADHD (e.g. with DSM-IV clinical symptom definitions), but there is no relationship to executive functions as measured by actual cognitive functions measured in performance tests. (For instance, tests of working memory do not agree with ratings of memory performance.
- Impairment of executive functions is common in many disorders other than ADHD, for example anxiety, depression, psychosis, etc. In fact, executive dysfunction cuts across almost all mental disorders and cognitive impairments. It would thus appear to be more a consequence of disorders than a specific cause of disorders.
- Finally, a number of investigations fail to find the executive dysfunctions postulated for ADHD.
For these reasons I believe that while it is useful to assess executive functions in ADHD, particularly since these functions may be trainable and coachable, a full assessment of ADHD requires a much broader range of symptoms and diagnostic criteria.
Tuesday, October 14, 2008
The myths of ADHD
Over the years I have encountered many skeptics who believe neither in medicating children nor in labeling and diagnosing them. Deep, instinctual protective feelings towards children become displayed as unwavering hostility to all who prescribe psychiatric medications or attach a label to children. Anti-labeling and anti-medication becomes a lifestyle, a religious quest, an angry flag-bearing march against psychiatrists, psychologists, pharmaceutical companies, and even government-sponsored research.
Books and diatribes about Ritalin nation, running on Ritalin, normal temperament, suppression of creativity, drug company conspiracies, myth of the hyperactive child, drugging into submission, medicalization of normal behavior, etc.—have all been part of the history of pediatrics and child psychiatry. More recently the attacks have broadened to include adult ADHD as well.
Unfortunately there is always a grain of truth in these arguments. There is indeed over-prescribing, some children whose behavior is merely at the extreme end of the normal curve of temperament, some children whose life situations make them hyperactive and whose environments are the real problem; some who become zombies in the classroom from over-dosing, and some pharmaceutical companies who use lax criteria and exaggerate the numbers and the successes in treating with their drugs. As I suggested earlier, there is indeed some over-treatment, over-diagnosis, sloppy research, big pharma skullduggery in collaboration with corrupt researchers—matters well-covered in the media and in blogs by reputable critics (see especially the blogs on the subject by Barney Carroll).
But the real world is complicated. Science may take a while to catch up with flawed opinions floating about in peoples' heads as if they were fact. We now know that there is also a degree of reality behind the diagnoses, brilliant successes with some of the treatments, justification for early interventions; that there are multiple genetic and environmental risk factors associated with many childhood psychiatric conditions.
Though not ready for clinical use as yet, and notwithstanding the excesses by fraudulent practitioners of neurofeedback or brain scanning, there are nevertheless sound neuroscience advances at all levels that attest to the reality of conditions like ADHD; true diseases whose definitions are based in the genetics, biochemistry, brain morphology, and physiology of modern science.
I also believe that there are many honest collaborations between pharmaceutical companies and rigorous scientists that have made tremendous progress possible in therapeutics and basic knowledge about psychiatric illness in children. That transparency and close oversight are needed in those collaborations seems obvious as well.
I am prompted to bring these issues up because I recently read what I think is the most convincing and brilliant conversion by a standard critic into a more thoughtful advocate for appropriate diagnosis and treatment: the blog by Judith Warner, which I highly recommend:
http://warner.blogs.nytimes.com/2007/03/01/second-thoughts/
There are many brilliant and thoughtful observers out there who have been self-assured critics of ADHD, thinking it all a set of myths, until they have such a child themselves, or run face to face with these children in the lives of family or friends. The more brilliant the opposition, the more stunning the conversion to the reality.
Books and diatribes about Ritalin nation, running on Ritalin, normal temperament, suppression of creativity, drug company conspiracies, myth of the hyperactive child, drugging into submission, medicalization of normal behavior, etc.—have all been part of the history of pediatrics and child psychiatry. More recently the attacks have broadened to include adult ADHD as well.
Unfortunately there is always a grain of truth in these arguments. There is indeed over-prescribing, some children whose behavior is merely at the extreme end of the normal curve of temperament, some children whose life situations make them hyperactive and whose environments are the real problem; some who become zombies in the classroom from over-dosing, and some pharmaceutical companies who use lax criteria and exaggerate the numbers and the successes in treating with their drugs. As I suggested earlier, there is indeed some over-treatment, over-diagnosis, sloppy research, big pharma skullduggery in collaboration with corrupt researchers—matters well-covered in the media and in blogs by reputable critics (see especially the blogs on the subject by Barney Carroll).
But the real world is complicated. Science may take a while to catch up with flawed opinions floating about in peoples' heads as if they were fact. We now know that there is also a degree of reality behind the diagnoses, brilliant successes with some of the treatments, justification for early interventions; that there are multiple genetic and environmental risk factors associated with many childhood psychiatric conditions.
Though not ready for clinical use as yet, and notwithstanding the excesses by fraudulent practitioners of neurofeedback or brain scanning, there are nevertheless sound neuroscience advances at all levels that attest to the reality of conditions like ADHD; true diseases whose definitions are based in the genetics, biochemistry, brain morphology, and physiology of modern science.
I also believe that there are many honest collaborations between pharmaceutical companies and rigorous scientists that have made tremendous progress possible in therapeutics and basic knowledge about psychiatric illness in children. That transparency and close oversight are needed in those collaborations seems obvious as well.
I am prompted to bring these issues up because I recently read what I think is the most convincing and brilliant conversion by a standard critic into a more thoughtful advocate for appropriate diagnosis and treatment: the blog by Judith Warner, which I highly recommend:
http://warner.blogs.nytimes.com/2007/03/01/second-thoughts/
There are many brilliant and thoughtful observers out there who have been self-assured critics of ADHD, thinking it all a set of myths, until they have such a child themselves, or run face to face with these children in the lives of family or friends. The more brilliant the opposition, the more stunning the conversion to the reality.
Wednesday, October 8, 2008
How many ADHD children and adults are out there?
My mentor, Leon Eisenberg, once commented that when we started out in the 1960's studying "hyperactive children" --now called ADHD--it was hard to convince anyone that they really existed or that it mattered. Especially doubtful were the British, led by their great scholar Michael Rutter. Now the schools and homes seem to be flooded by them, to the point of an epidemic.
Although my old colleague Paul Wender, also at Hopkins in the 1960's, had first alleged that adults also had ADHD, nobody took that idea seriously until recently. Now there is a claim that their prevalence even exceeds the 2 to 3 percent of child ADHD, and over the last 5 years their prevalence has steadily and rapidly increased. Recently the National Comorbidity Survey of the World Health Organization (WHO) under a brilliant Harvard scholar, Ron Kessler, has placed the figure at 4 to 5 percent whereas the estimates for childhood ADHD average around 2 to 4 percent. What gives? Can there be more adult ADHD than child ADHD?
First, there are now dozens of studies throughout the world that consistently place childhood ADHD as high as 10 percent of the population, and averaging round 4 to 6 percent. Are there really 10 kids out of a hundred with ADHD (3 or 4 in every average classroom)?
Well how does one KNOW? Remember that these studies usually involve hundreds or thousands of children, so that defining a case cannot usually involve individual clinical interviews. Instead, they may involve telephone surveys, checklists of symptoms, or surveys of parents. Remember too, that according to the standard psychiatric definition (the Diagnostic and Statistical Manual of the American Psychiatric Association, now in its 4th revision, called DSM-4), there are 5 criteria that must be met.
The most important of those criteria is the one that requires that the symptoms not be better explained by some other illness; that is, a "differential diagnosis" must be made. If it's autism, or depression, or anxiety, etc., then the 18 ADHD symptoms could be caused by one of these other illnesses. But wait! Doesn't that mean you have to do a COMPLETE psychiatric examination? If you don't then the presumed "case" of ADHD could be something else, and the total count of ADHD cases would include all the other possible diagnostic contenders.
Now examining all of the epidemiological studies of ADHD, the only one that I know of that actually used a complete diagnostic interview on enough children to form a reliable prevalence estimate was a study by Adrian Angold and Jane Costello in the Western counties of North Carolina. Their prevalence rate for ADHD: less than 2 percent. Incidentally, they found that a great many children who did NOT meet ADHD criteria were being treated for it, and a great many who DID meet criteria were not being treated for it. Obviously a correct diagnosis is necessary to avoid both kinds of mistakes.
Wow! ADHD IS BOTH UNDERESTIMATED AND OVERESTIMATED at the same time, and they are being unter-treated and over-treated at the same time.
Now what about the adults? The big problem here is that there are no agreed-upon criteria for adult ADHD, though there is much work being done to alter the criteria to account for developmental changes in symptomatology, age of onset, and types of impairment associated with the condition. DSM-V will undoubtedly give us the basis for a real epidemiologic survey.
However, the afore-mentioned WHO study started with a subsample of the very large survey carried out around the world, and by using statistical methods (e.g. imputing the actual numbers for the whole sample from a smaller subsample), they used 6 symptoms that were included in the original survey, to arrive at a prevalence estimate for adult ADHD, based on followup telephone interviews of the smaller subsample. The result: 4 to 6 percent prevalence of adult ADHD.
Here again, there really is no full psychiatric interview, so that in my mind these high figures must remain suspect. Incidentally, I am not reassured by the fact that this "WHO Study", which I participated in, was sponsored in part by a drug company, and that shortly after the first findings the drug company was using the 6 symptoms as a diagnostic guide for recommending adults to see their physician for possible treatment.
So here we have another possible explanation of the explosive growth of adult ADHD: it is a boon for pharmaceutical companies who are now virtually all scrambling to get FDA approval for ADHD drugs in children to be approved for adults as well.
Don't get me wrong; adult ADHD is a real problem, and one that can be successfully treated by medication and other methods, and is a condition that has serious consequences for the patient and their families. But if ADHD, as we and most scientists agree, is a developmental problem starting early in life, then it seems unlikely that the true prevalence for adults can be more than the prevalence for children.
Adults will pass through the age of risk for many other psychiatric and emotional conditions than for children, so that they will have more comorbidities and more impact on their adult lives than they did as children. On the whole they could be sicker, though many compensate or adjust to their illness, especially those well-treated as children. But it is precisely these other conditions which might better explain their illness and dysfunctions, so they may be mis-diagnosed as ADHD when they are not ADHD cases at all, just as many children have likewise been mis-diagnosed because their symtoms could be due to other disorders that were not screened for.
The bottom line: symptoms alone do not define ADHD. It is a mistake to make the diagnosis without carefully ruling out other explanations. To do this requires a sound clinical interview by a trained mental health professional.
Although my old colleague Paul Wender, also at Hopkins in the 1960's, had first alleged that adults also had ADHD, nobody took that idea seriously until recently. Now there is a claim that their prevalence even exceeds the 2 to 3 percent of child ADHD, and over the last 5 years their prevalence has steadily and rapidly increased. Recently the National Comorbidity Survey of the World Health Organization (WHO) under a brilliant Harvard scholar, Ron Kessler, has placed the figure at 4 to 5 percent whereas the estimates for childhood ADHD average around 2 to 4 percent. What gives? Can there be more adult ADHD than child ADHD?
First, there are now dozens of studies throughout the world that consistently place childhood ADHD as high as 10 percent of the population, and averaging round 4 to 6 percent. Are there really 10 kids out of a hundred with ADHD (3 or 4 in every average classroom)?
Well how does one KNOW? Remember that these studies usually involve hundreds or thousands of children, so that defining a case cannot usually involve individual clinical interviews. Instead, they may involve telephone surveys, checklists of symptoms, or surveys of parents. Remember too, that according to the standard psychiatric definition (the Diagnostic and Statistical Manual of the American Psychiatric Association, now in its 4th revision, called DSM-4), there are 5 criteria that must be met.
The most important of those criteria is the one that requires that the symptoms not be better explained by some other illness; that is, a "differential diagnosis" must be made. If it's autism, or depression, or anxiety, etc., then the 18 ADHD symptoms could be caused by one of these other illnesses. But wait! Doesn't that mean you have to do a COMPLETE psychiatric examination? If you don't then the presumed "case" of ADHD could be something else, and the total count of ADHD cases would include all the other possible diagnostic contenders.
Now examining all of the epidemiological studies of ADHD, the only one that I know of that actually used a complete diagnostic interview on enough children to form a reliable prevalence estimate was a study by Adrian Angold and Jane Costello in the Western counties of North Carolina. Their prevalence rate for ADHD: less than 2 percent. Incidentally, they found that a great many children who did NOT meet ADHD criteria were being treated for it, and a great many who DID meet criteria were not being treated for it. Obviously a correct diagnosis is necessary to avoid both kinds of mistakes.
Wow! ADHD IS BOTH UNDERESTIMATED AND OVERESTIMATED at the same time, and they are being unter-treated and over-treated at the same time.
Now what about the adults? The big problem here is that there are no agreed-upon criteria for adult ADHD, though there is much work being done to alter the criteria to account for developmental changes in symptomatology, age of onset, and types of impairment associated with the condition. DSM-V will undoubtedly give us the basis for a real epidemiologic survey.
However, the afore-mentioned WHO study started with a subsample of the very large survey carried out around the world, and by using statistical methods (e.g. imputing the actual numbers for the whole sample from a smaller subsample), they used 6 symptoms that were included in the original survey, to arrive at a prevalence estimate for adult ADHD, based on followup telephone interviews of the smaller subsample. The result: 4 to 6 percent prevalence of adult ADHD.
Here again, there really is no full psychiatric interview, so that in my mind these high figures must remain suspect. Incidentally, I am not reassured by the fact that this "WHO Study", which I participated in, was sponsored in part by a drug company, and that shortly after the first findings the drug company was using the 6 symptoms as a diagnostic guide for recommending adults to see their physician for possible treatment.
So here we have another possible explanation of the explosive growth of adult ADHD: it is a boon for pharmaceutical companies who are now virtually all scrambling to get FDA approval for ADHD drugs in children to be approved for adults as well.
Don't get me wrong; adult ADHD is a real problem, and one that can be successfully treated by medication and other methods, and is a condition that has serious consequences for the patient and their families. But if ADHD, as we and most scientists agree, is a developmental problem starting early in life, then it seems unlikely that the true prevalence for adults can be more than the prevalence for children.
Adults will pass through the age of risk for many other psychiatric and emotional conditions than for children, so that they will have more comorbidities and more impact on their adult lives than they did as children. On the whole they could be sicker, though many compensate or adjust to their illness, especially those well-treated as children. But it is precisely these other conditions which might better explain their illness and dysfunctions, so they may be mis-diagnosed as ADHD when they are not ADHD cases at all, just as many children have likewise been mis-diagnosed because their symtoms could be due to other disorders that were not screened for.
The bottom line: symptoms alone do not define ADHD. It is a mistake to make the diagnosis without carefully ruling out other explanations. To do this requires a sound clinical interview by a trained mental health professional.
Wednesday, September 24, 2008
Science or Scam: Neuro-imaging for ADHD?
More than a dozen years or so ago I was attending a conference in Israel on ADHD when one of the organizers--a neurologist-- asked me to please address the problem of Dr. Daniel Amen's claims about his subtyping of ADHD through the use of the SPECT imaging technology. The problem she said, was that many of her patients were flying from Israel to the U.S. in order to be "subtyped" and then treated by Dr. Amen in California.
Single photon emission computed tomography (SPECT)) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient. One disadvantage of this technology, in contrast to MRI or fMRI, is that it requires giving a dose of a radioactive tracer.
In response to Dr. Amen's talk I asked to see any data supporting his claims. He responded by saying that he had over 12,000 cases on which to base his typology. "What statistical methods did you use?" I asked. He replied that they had not been published yet, but that researchers like me would have to undertake such a huge job.
More recently, 11 years later in La Jolla, California I happened to be on a panel with Dr. Amen and the same issue was raised about publications. He responded that there was now a publication, but he didn't recall the name of the journal; but he asked one of his colleagues in the audience for the name. The colleague looked puzzled, threw up his arms quizzically, and said he didn't know. So much for supportive scientific proof.
A prominent neurologist and imaging researcher, George Busch, M.D. happened to be on the same panel. He unequivocally denounced Dr. Amen's claims and asserted that no respectable scientist had yet to find a way to use neuro-imaging to make those clinical subtype distinctions, let alone a diagnosis. Work by Jay Giedde, Judy Rapaport, and Javier Castellanos at NIMH with MRI and fMRI have indeed shown that there are important brain differences between ADHD and normal controls, both cross-sectionally and developmentally. But no one claims that any diagnostic rules from those data are capable of the precision required to beat clinical assessments.
Here's what Dr. Amen claims about ADHD subtypes:
Type 1 — Classic ADHD. Symptoms such as short attention span, distractibility, disorganization, procrastination, poor internal supervision plus hyperactivity and impulsivity.* Type 2 — Inattentive ADHD. Classic ADHD symptoms, but instead of hyperactivity, there is low energy.* Type 3 — Overfocused ADHD. Classic ADHD symptoms as well as negative thoughts and behaviors, such as opposition and arguing.* Type 4 — Temporal Lobe ADHD. Classic ADHD symptoms plus irritability, aggressiveness, and memory and learning problems.* Type 5 — Limbic ADHD. Combines ADHD with depression and low energy and decreased motivation.* Type 6 — The Ring of Fire. Cross between ADHD and bipolar disorder. Characterized by moodiness, aggressiveness, and anger.
Now any experienced clinician will undoubtedly agree that these are recognizable forms of presentation at a child clinic. In fact, these are classic descriptions from the literature: the hyperactive/impulsive type; the inattentive type; the overfocused type (e.g. Kinsbourne's type); the hypoactive type, etc. But are these "types" confirmed by an appropriate methodology as variants of ADHD? Where is the cluster analysis or factor analysis of large samples characterized through rigorous clinical documentation? Where are the structured or unstructured interviews and histories to validate the diagnosis? What are the statistical boundaries among these so-called types? What is the evidence that they respond differently to treatments or have other biological or genetic markers to distinguish them?
If I had 12,000 cases in my database, I would not waste a day before exploring the typologies that might be hidden there. Amen's work is classic quasi-scientific mystification: the failure to distinguish between anecdotes and data, and between hypothesis and fact.
Like all fringe quasi-scientific appeals to a needy public, there are classic signs of when the patients are being fooled:
1) There is an impressive and truly science-based technology, so sophisticated that the ordinary public must take the claims on faith;
2) The proponent of this new method, though possibly trained in traditional clinical and scientific paths, breaks with the majority of scientists and fails to pass the test of peer review;
3) The proponent himself (or herself) is too busy seeing patients and collecting large fees to do the necessary research themselves;
4) The proponent tirelessly appears at conferences and seminars worldwide, and develops an adoring but uninformed following despite repeated criticisms to produce real data;
5) Standard treatments are often the outcome from the elaborate workups and tests, though actual followup studies are seldom provided.
I have to admit that personally Dr. Amen is charming, well-informed, and well-trained. He gives a convincing talk, and if I were an uninformed normal patient, I would probably agree that there is no definitive biological test for ADHD, no pathogonomic sign, and a truly complex clinical picture. I might possibly end up in desperation spending thousands of dollars after seeing the lovely colored pictures of the brain, with hot spots where ADHD resides. But fortunately, I have been around long enough to spot mumbo-jumbo when I see it. Let the buyer beware.
Single photon emission computed tomography (SPECT)) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient. One disadvantage of this technology, in contrast to MRI or fMRI, is that it requires giving a dose of a radioactive tracer.
In response to Dr. Amen's talk I asked to see any data supporting his claims. He responded by saying that he had over 12,000 cases on which to base his typology. "What statistical methods did you use?" I asked. He replied that they had not been published yet, but that researchers like me would have to undertake such a huge job.
More recently, 11 years later in La Jolla, California I happened to be on a panel with Dr. Amen and the same issue was raised about publications. He responded that there was now a publication, but he didn't recall the name of the journal; but he asked one of his colleagues in the audience for the name. The colleague looked puzzled, threw up his arms quizzically, and said he didn't know. So much for supportive scientific proof.
A prominent neurologist and imaging researcher, George Busch, M.D. happened to be on the same panel. He unequivocally denounced Dr. Amen's claims and asserted that no respectable scientist had yet to find a way to use neuro-imaging to make those clinical subtype distinctions, let alone a diagnosis. Work by Jay Giedde, Judy Rapaport, and Javier Castellanos at NIMH with MRI and fMRI have indeed shown that there are important brain differences between ADHD and normal controls, both cross-sectionally and developmentally. But no one claims that any diagnostic rules from those data are capable of the precision required to beat clinical assessments.
Here's what Dr. Amen claims about ADHD subtypes:
Type 1 — Classic ADHD. Symptoms such as short attention span, distractibility, disorganization, procrastination, poor internal supervision plus hyperactivity and impulsivity.* Type 2 — Inattentive ADHD. Classic ADHD symptoms, but instead of hyperactivity, there is low energy.* Type 3 — Overfocused ADHD. Classic ADHD symptoms as well as negative thoughts and behaviors, such as opposition and arguing.* Type 4 — Temporal Lobe ADHD. Classic ADHD symptoms plus irritability, aggressiveness, and memory and learning problems.* Type 5 — Limbic ADHD. Combines ADHD with depression and low energy and decreased motivation.* Type 6 — The Ring of Fire. Cross between ADHD and bipolar disorder. Characterized by moodiness, aggressiveness, and anger.
Now any experienced clinician will undoubtedly agree that these are recognizable forms of presentation at a child clinic. In fact, these are classic descriptions from the literature: the hyperactive/impulsive type; the inattentive type; the overfocused type (e.g. Kinsbourne's type); the hypoactive type, etc. But are these "types" confirmed by an appropriate methodology as variants of ADHD? Where is the cluster analysis or factor analysis of large samples characterized through rigorous clinical documentation? Where are the structured or unstructured interviews and histories to validate the diagnosis? What are the statistical boundaries among these so-called types? What is the evidence that they respond differently to treatments or have other biological or genetic markers to distinguish them?
If I had 12,000 cases in my database, I would not waste a day before exploring the typologies that might be hidden there. Amen's work is classic quasi-scientific mystification: the failure to distinguish between anecdotes and data, and between hypothesis and fact.
Like all fringe quasi-scientific appeals to a needy public, there are classic signs of when the patients are being fooled:
1) There is an impressive and truly science-based technology, so sophisticated that the ordinary public must take the claims on faith;
2) The proponent of this new method, though possibly trained in traditional clinical and scientific paths, breaks with the majority of scientists and fails to pass the test of peer review;
3) The proponent himself (or herself) is too busy seeing patients and collecting large fees to do the necessary research themselves;
4) The proponent tirelessly appears at conferences and seminars worldwide, and develops an adoring but uninformed following despite repeated criticisms to produce real data;
5) Standard treatments are often the outcome from the elaborate workups and tests, though actual followup studies are seldom provided.
I have to admit that personally Dr. Amen is charming, well-informed, and well-trained. He gives a convincing talk, and if I were an uninformed normal patient, I would probably agree that there is no definitive biological test for ADHD, no pathogonomic sign, and a truly complex clinical picture. I might possibly end up in desperation spending thousands of dollars after seeing the lovely colored pictures of the brain, with hot spots where ADHD resides. But fortunately, I have been around long enough to spot mumbo-jumbo when I see it. Let the buyer beware.
Tuesday, September 16, 2008
Fish Oil as a treatment for ADHD?
Some physicians are now recommending fish oil in the form of omega-3 fatty acids or PUFAs (Poly-unsaturated fatty acids) as a therapy for ADHD children, adolescents and adults. This is partly in response to the persisting fears of parents about stimulant medications and partly on the basis of the always-hopeful findings in the literature, i.e. on the basis of inconclusive studies that "suggest further research is needed."
As in most alternative therapies, some elements of basic neuroscience are cited as the rationale for the therapy, followed by "preliminary studies" which give hopeful signs (one might cynically say especially signs of future funding from government or pharmaceutical companies). In this case there are a number of animal studies which compare spontaneously hyperactive rats with their cool Sprague-Dawley cousins, who show signs of better cognition after dietary supplementation with PUFAs. Also, it appears that lack of these fatty acids are known to impede neural development in young babies.
However, as for the scientific rationale, one respectable scientist says that, "...our current understanding of the importance of essential fatty acids (EFAs) and their metabolites to optimal brain function is based on an enormously complex set of interlinked biochemical, neurological, and laboratory observations. The applicability of these research findings to children with attention-deficit/hyperactivity disorder (ADHD) is unknown." (Betsy Busch, Polyunsaturated fatty acid supplementation for ADHD? Fishy, fascinating, and far from clear. J. Devel. & Behav. Pediatrics, Vol 28(2) Apr 2007, 139-144).
What about clinical trials? One comprehensive recent review (E.H. Clayton, et al., Acta Neuropsychiatrica, Vol 19(2) Apr 2007, 92-103) found that 4 randomized controlled trials showed uncertain benefit for ADHD and no benefit for autism and bipolar disorder.
A typical research story is illustrated from a controlled trial by A. Richardson and colleagues, who studied 41 children with ADHD and LD randomly assigned to highly unsaturated fatty acids (HUFAs) or placebo for 12 weeks. They found a mean improvement on 7 of 14 parent rating scales, "reaching significance levels on 3 of 14 scales." (Progress in Neuro-Psychopharm. & Biol. Psychiat. Vol 26, 2002, 233-39) Of course, they did not adjust for multiple tests, so technically the results are nil, but they call for further research.. By 2006, when reviewing the field, the same author concludes, "Omega-3 is not supported by current evidence as a primary treatment for ADHD or related conditions...." but still calls for further research. (A.J. Richardson, Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int. Rev. Psychiat. Vol 18, April 2006, 155-172).
Well, this is merely the research game as we have come to know it. I too have been enticed by small pilot studies that lead to larger grants (as in my flirtation with the Feingold diet studies, though there I took satisfaction in stopping a national trend sweeping the country which was diverting many parents from worthwhile treatments).
One final research note on the dietary studies that also applies to drug trials involving parents and children. Many of these trials use apparently blind judgments by the physician which are in turn based upon reports by parents. But virtually all drugs create subjective awarenness by the patient that something is happening, and patients follow the demand characteristics of the experiment to give some response they think is expected, and parents as well as physicians become aware of side effects which allows a peek through the double blind. Note that in the previous study above the effects were found in parents but not by teachers (who are generally much more unaware of side effects and subjective bodily changes). When a trial shows parent reported changes but not teacher reported changes, one needs to be very suspicious about the signficance of any positive findings. All of those physicians out there who use the DSM-IV rating scale or global judgments as their outcome measures are likely to be subject to a positive bias about the drug being studied. After all, they get paid by the pharmaceutical companies and there is strong incentive to produce positive results and continued study.
I have made this point many times at advisory committee meetings, but I have yet to find a single pharmaceutical company that pays attention to the suggestion of using blind raters who are separate from the physicians controlling the monitoring for side effects or adverse reactions.
My conclusion from reviewing the literature on Fish Oil as therapy for ADHD is that it clearly is not proven. There are two therapies supported by research over a 40 year period: the combination of behavioral management (both in the classroom and at home); and stimulant drugs.
But I make the following observation from my practice: it is usually quite useless to argue with a parent when they are predisposed against the use of drugs, no matter how noxious the child's behavior has become in their own lives. For those parents I make a therapeutic alliance by saying, sure, there are dietary therapies. First, make sure your child has a well-balanced diet, especially limiting their preference for high carb foods, and making sure there is plenty of protein at breakfast (I give them a pretty good story from our studies on this subject).
I take a dietary history and recommend a 3-day diet diary, recording everything the child eats, and use it to steer the child and family away from obvious imbalances (there is good evidence that ad liibidem access to carbohydrates leads to an over use of them, especially in ADHD and Conduct-Disordered kids). I recommend limited access to sugar and sweets, but always balancing them with protein. For adolescents I am especially cautious about caffienated drinks.
Eventually most parents return to the clinic after a few weeks saying, "Yes he (or she) is much better! But, you know, it's still a problem. What else can I do? I still don't want Ritalin."
"Ahem, Madam, I agree and I can recommend a great medicine that is not Ritalin! (Well, it might be Metadate or Focalin or Adderall or Concerta or one of the other possibilities down the line when those don't work. But see my physician colleague, he (or she) knows all about it and can give you the latest medicine that works...") You get my drift. Since I do not myself prescribe, I rely on my savvy physician colleagues to know about the MTA study and the nuances of psychopharmacology that make for an effective treatment plan over the entire lifespan. (More on the MTA study in future postings.)
As in most alternative therapies, some elements of basic neuroscience are cited as the rationale for the therapy, followed by "preliminary studies" which give hopeful signs (one might cynically say especially signs of future funding from government or pharmaceutical companies). In this case there are a number of animal studies which compare spontaneously hyperactive rats with their cool Sprague-Dawley cousins, who show signs of better cognition after dietary supplementation with PUFAs. Also, it appears that lack of these fatty acids are known to impede neural development in young babies.
However, as for the scientific rationale, one respectable scientist says that, "...our current understanding of the importance of essential fatty acids (EFAs) and their metabolites to optimal brain function is based on an enormously complex set of interlinked biochemical, neurological, and laboratory observations. The applicability of these research findings to children with attention-deficit/hyperactivity disorder (ADHD) is unknown." (Betsy Busch, Polyunsaturated fatty acid supplementation for ADHD? Fishy, fascinating, and far from clear. J. Devel. & Behav. Pediatrics, Vol 28(2) Apr 2007, 139-144).
What about clinical trials? One comprehensive recent review (E.H. Clayton, et al., Acta Neuropsychiatrica, Vol 19(2) Apr 2007, 92-103) found that 4 randomized controlled trials showed uncertain benefit for ADHD and no benefit for autism and bipolar disorder.
A typical research story is illustrated from a controlled trial by A. Richardson and colleagues, who studied 41 children with ADHD and LD randomly assigned to highly unsaturated fatty acids (HUFAs) or placebo for 12 weeks. They found a mean improvement on 7 of 14 parent rating scales, "reaching significance levels on 3 of 14 scales." (Progress in Neuro-Psychopharm. & Biol. Psychiat. Vol 26, 2002, 233-39) Of course, they did not adjust for multiple tests, so technically the results are nil, but they call for further research.. By 2006, when reviewing the field, the same author concludes, "Omega-3 is not supported by current evidence as a primary treatment for ADHD or related conditions...." but still calls for further research. (A.J. Richardson, Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int. Rev. Psychiat. Vol 18, April 2006, 155-172).
Well, this is merely the research game as we have come to know it. I too have been enticed by small pilot studies that lead to larger grants (as in my flirtation with the Feingold diet studies, though there I took satisfaction in stopping a national trend sweeping the country which was diverting many parents from worthwhile treatments).
One final research note on the dietary studies that also applies to drug trials involving parents and children. Many of these trials use apparently blind judgments by the physician which are in turn based upon reports by parents. But virtually all drugs create subjective awarenness by the patient that something is happening, and patients follow the demand characteristics of the experiment to give some response they think is expected, and parents as well as physicians become aware of side effects which allows a peek through the double blind. Note that in the previous study above the effects were found in parents but not by teachers (who are generally much more unaware of side effects and subjective bodily changes). When a trial shows parent reported changes but not teacher reported changes, one needs to be very suspicious about the signficance of any positive findings. All of those physicians out there who use the DSM-IV rating scale or global judgments as their outcome measures are likely to be subject to a positive bias about the drug being studied. After all, they get paid by the pharmaceutical companies and there is strong incentive to produce positive results and continued study.
I have made this point many times at advisory committee meetings, but I have yet to find a single pharmaceutical company that pays attention to the suggestion of using blind raters who are separate from the physicians controlling the monitoring for side effects or adverse reactions.
My conclusion from reviewing the literature on Fish Oil as therapy for ADHD is that it clearly is not proven. There are two therapies supported by research over a 40 year period: the combination of behavioral management (both in the classroom and at home); and stimulant drugs.
But I make the following observation from my practice: it is usually quite useless to argue with a parent when they are predisposed against the use of drugs, no matter how noxious the child's behavior has become in their own lives. For those parents I make a therapeutic alliance by saying, sure, there are dietary therapies. First, make sure your child has a well-balanced diet, especially limiting their preference for high carb foods, and making sure there is plenty of protein at breakfast (I give them a pretty good story from our studies on this subject).
I take a dietary history and recommend a 3-day diet diary, recording everything the child eats, and use it to steer the child and family away from obvious imbalances (there is good evidence that ad liibidem access to carbohydrates leads to an over use of them, especially in ADHD and Conduct-Disordered kids). I recommend limited access to sugar and sweets, but always balancing them with protein. For adolescents I am especially cautious about caffienated drinks.
Eventually most parents return to the clinic after a few weeks saying, "Yes he (or she) is much better! But, you know, it's still a problem. What else can I do? I still don't want Ritalin."
"Ahem, Madam, I agree and I can recommend a great medicine that is not Ritalin! (Well, it might be Metadate or Focalin or Adderall or Concerta or one of the other possibilities down the line when those don't work. But see my physician colleague, he (or she) knows all about it and can give you the latest medicine that works...") You get my drift. Since I do not myself prescribe, I rely on my savvy physician colleagues to know about the MTA study and the nuances of psychopharmacology that make for an effective treatment plan over the entire lifespan. (More on the MTA study in future postings.)
Subscribe to:
Posts (Atom)
