Modafinil: An alternative treatment for ADHD and comorbid substance abuse?

Can Modafinil (Provigil) Replace Stimulant Medications in Adult ADHD where stimulant drug abuse is a concern?

It is a Catch-22 of the ADHD world. An individual is suffering from severe ADHD symptoms and appropriate stimulant medications may help remedy some of the negative side effects of the disorder. However, due to the high prevalence of substance abuse in ADHD (some officials put the rate of comorbid substance abuse as high as to 30% in the ADHD population), including stimulant medications such as amphetamines, treatment of ADHD symptoms via stimulant medications cannot, by nature of the comorbid substance abuse disorder, be a treatment option.

The appearance of (relatively) novel non-stimulant medication alternatives such as Strattera (atomoxetine), have offered individuals with ADHD another treatment alternative. However, the results are often mixed. Strattera often works well with the inattentive-dominated forms of the disorder, but the positive results are often not as pronounced for the more hyperactive or impulsive forms of ADHD, especially if comorbid disorders such as conduct-related issues surface.

Another alternative may be a completely different type of drug, which, while not a stimulant in its own right, can act on or exhibit pseudo-stimulant properties. It appears that in at least some cases, Modafinil (Provigil) may be the type of drug we're looking for in these cases.

**Blogger's note: The extent of the study highlighting this case for Modafinil treatment for ADHD and comorbid amphetamine abuse is intended for adult treatment only. Given the relative scarcity of research on medication options for adult ADHD symptoms (compared to those designed more for children), this post is designed for offering a possible treatment alternative for ADHD in adults. Nevertheless, some recent studies have shown promising results of Modafinil as an ADHD treatment method for children and adolescents.

It is important to note, that while not initially designed as an ADHD-specific medication (and not a stimulant in its own right), Modafinil does share at least some degree of overlap with several stimulant agents for ADHD treatment. One is its regulation of catecholamines (important neuro-signaling chemical agents, whose balance in and out of neuronal cells is crucially important for regulating attention, hyperactive and impulsive behaviors, and locomotor control). As far as its mode of action and metabolism (clinical pharmacokinetics of Modafinil) are concerned, drug-drug interactions between Modafinil and several ADHD stimulant medications such as methylphenidate or dexamphetamine (Dexedrine) appear to be limited.

A background note on addiction potentials of ADHD drugs: This section is an aside, and is meant to serve as some background information and to clear up potential confusion surrounding ADHD medications and their addiction potentials. The next four paragraphs may be skipped if you are pressed for time.

While I cannot stress enough the importance of regulating neuro-chemical balance for both the onset of ADHD as well as drug addiction (which are affected by pharmacological agents such as ADHD medications, in varying forms), it is the rate of action for which these chemical changes take place which typically drives a particular drug's addiction potential.

Unfortunately, this last fact is often lost in much of the literature surrounding ADHD treatment (especially those which promote non-pharmaceutical treatments for the disorder). For example, many "natural" ADHD treatment books and websites frequently start out by asserting (erroneously) that methylphenidate is the equivalent of crack cocaine, and promotes later drug abuse and addiction.

While this blogger is a personal advocate for natural approaches to treating ADHD whenever possible (and without compromising overall treatment effectiveness in ADHD treatment), he wants to make it clear that significant differences do exist between ADHD medications and stimulant street drugs. One of the most telling signs of this is the rate of uptake and clearance of drug-like agents into and out of the brain, respectively. In general, the quicker a substance is taken up into the central nervous system and the faster it clears the brain, the more likely this chemical agent will elicit a "high" and an increased tendency towards substance dependence.

ADHD medications like Ritalin, while having some degree of overlap in structure and net effects of action as cocaine, are specifically designed to have a much slower rate of release and clearance, significantly reducing their abuse potential compared to cocaine. We have previously discussed Ritalin (methylphenidate) vs. cocaine addiction potentials in earlier posts.


Modafinil: Modes of action and addiction potential:

The reason I am providing all of this information is the fact that the successful regulation and softening of rapid spikes and clearances of chemical peaks is a crucial component to curbing the drug addiction process. It is believed that modafinil may work so well at reducing drug cravings by targeting this very mechanism. Unlike many stimulant medications which can produce some type of "high" (especially if abused by snorting or injection, or taken at abnormally high doses), Modafinil has a low abuse potential, and offers several other advantages over methylphenidate.

Modafinil does have a relatively positive track record for mitigating substance abuse disorders. For example, the administration of Modafinil can attenuate cocaine dependence. In contrast, methylphenidate (Ritalin, Concerta, Metadate, Daytrana), while being very effective as an ADHD treatment, does little to curb comorbid substance abuse disorders in ADHD patients. Unfortunately, the effectiveness of Modafinil on treating comorbid substance abuse disorders in individuals with ADHD may be limited to specific drugs. For example similar positive effects of Modafinil on nicotine dependence appear to be less pronounced.

Modafinil may also offer advantages over traditional stimulants as well. As a cognitive enhancement type of pharmacological agent, modafinil may be useful in improving the work performance of adults with ADHD by improving short-term memory and visual recall, impulse control, and spatial skills (all of which are frequent deficits in children and adults with ADHD). Additionally, similar improvements were seen in individuals with schizophrenia, suggesting the diversity of modafinil's range of performance in cognitive improvement. These improvements are typically not seen in individuals unaffected by psychological disorders, further supporting the evidence that modafinil is less likely to be abused recreationally in the general population.

The potential implications of modafinil for ADHD treatment may be further reaching than the details outlined in the original article (and basis of this post, highlighting the effects of modafinil on amphetamine abuse in adult ADHD). For example, modafinil, as a vigilance-promoting medication, can offset an afternoon dip in arousal state (which has implications on many of the shorter-acting stimulant medications, which begin to wear off around this time). This may be useful for individuals with sleep disorders (which are common in ADHD), as well as regulating circadian rhythms. In a post earlier this month, we investigated the relationship between ADHD and seasonal affective disorders, and hinted at the association between ADHD and disruption in circadian rhythms.


Potential future implications of Modafinil as an ADHD treatment alternative:

Additionally, while Modafinil may offer benefits for the whole ADHD spectrum, this blogger hypothesizes that it may be most useful for treating the inattentive subtype of the disorder. Some reasons for this are as follows:

• Activity patterns and circadian rhythms may often be associated with ADHD subtype. For example, "morning people" with ADHD may have a tendency to fall into the more hyperactive/impulsive group, while "eveningness" is more of an inattentive ADHD trait, suggesting more of a disruption in the circadian rhythms of inattentive ADHD'ers.
• Additionally, non-stimulants often have somewhat of a better track record with the inattentive subtype of ADHD compared to the more hyperactive/impulsive subtypes. The uses of the non-stimulant atomoxetine (Strattera), highlight this general trend. While atomoxetine treatments often result in drastic improvements in all ADHD subtypes, negative side effects are often less seen in the inattentive subtype.
• Compared to stimulants, non-stimulant medications for ADHD often do a better job at not exacerbating comorbid disorders such as obsessive compulsive or anxiety disorders (which are often more common to the ADHD inattentive subtype). Additionally, Modafinil treatment can be useful in treating adults with ADHD and a history of mood disorders.
• Modafinil offers advantages over methylphenidate as far as fewer side effects including appetite suppression, sleep disturbances and heart rate dysfunction (orthostatic tachycardia, which essentially is significant changes in heart rhythms based on postural changes, such as standing up quickly from a seated position).
• Anecdotal evidence, as noted by the Modafinil and amphetamine abuse study mentioned earlier, also suggests that Modafinil may be a useful treatment method for "refractory" cases, or individuals who have consistently shown poor response to other treatment medications and interventionary measures.
  
• Finally, it is important to note (and this was also touched on in the Modafinil and amphetamine abuse study), that Modafinil treatment may be better suited for the more "controlled" abusers of stimulants. In other words, better effects might be seen for adults who regularly take illegal stimulant drugs such as amphetamines as a conscious effort to "self-medicate" for their ADHD, as opposed to an out-of-control drug addict who craves the drugs on a non-scheduled basis.

Given the high propensity of comorbid disorders when deciding on treatment for ADHD, as well as practicality issues concerning the administration of medicinal agents for treatment of the disorder in adults, I see a fair amount of potential for Modafinil's "off-label" usage as a treatment alternative to stimulants in adults with ADHD.

Does Blood Type Affect ADHD?

This blog has often discussed the wide range of genetic influences on ADHD and related disorders. Some of the ADHD genes we have previously investigated include:

• DAT1 gene (often referred to simply as "DAT", possibly related to Tourette's and eating disorders such as bulimia)
• MAOA gene (likely has gender-specific effects, also tied to autism, bipolar and anxiety disorders)
• COMT gene (can affect dosage levels of ADHD stimulant medications, and possibly have an impact on brain regions responsible for attentional control)
• SLC6A2 gene (also called "NET" or "norepinephrine transporter gene", may affect the response to Strattera, also related to posture and eating disorders such as anorexia)
• SLC6A4 gene (often has a greater potential effect on males with ADHD, associated with autism)
• Protogenin gene (possibly related to ADHD and reading disabilities)
• DRD4 gene (also may be related to schizophrenia, alcoholism, and resistance to Parkinson's)
• Fatty acid desaturase genes (may play a role in deficiencies in omega-3 levels in ADHD)
• CREM gene (may be related to hormonal regulation, including the sleep-related melatonin)
• Serotonin receptor 1B gene (may be more associated with the inattentive subtype of ADHD)

Additionally, some of these genes may work together in combo. For example, a combination of specific variations in the DAT1 gene and the DRD4 gene may associate with IQ and behavioral disorders as they relate to ADHD.

The main point of all of these examples was not to overwhelm anyone, but rather to highlight the intricate relationship between genetics and ADHD heritability.

Adding to this extensive list may be a new set of genes related to blood types and ADHD.

**For a quick synopsis of blood types, please consult the italicized paragraphs below. Otherwise you may skip to the next paragraph highlighting a new study on blood type and ADHD.

Human blood types are often classified by the "ABO" system. "A" and "B" refer to immune-regulating factors and play a major role in blood transfusions. These blood types are acquired from our parents and can come in dominant and recessive forms. Genes for blood type can be found on the 9th human chromosome.

They are the two main (or dominant) forms of immune-regulating blood factors. Additionally, A and B can be "codominant", that is an individual can have a mixture of the two. For these "codominant" individuals, their blood type is labeled "AB". If an individual has neither "A" nor "B", he or she is labeled as an "O".

In essence, if you have a specific letter(s), you can donate blood to individuals who share your same letters (there are actually other important factors and donor restrictions besides this, such as the "Rh factor", but for sake of simplicity, we will just discuss "ABO" for the moment). For example, a person with type "A" blood could donate to another person who has "A" or "AB" because both "A" and "AB" would recognize the "A" component. They could not donate to a "B" or an "O" blood type because these individuals' bodies would not be able to recognize the "A", resulting in a severe immuno-rejection problem.

An "O" could donate to and "A", a "B", an "AB", or another "O" (again, there are detailed exceptions to this generalization), because "O" does not have either of the "A" or "B" markers on it, so the recipient's body would not see anything "foreign" about this. This makes "O" carriers better candidates for blood donation. On the flip side, and individual with type "AB" could take blood from and "A", a "B", an "AB" or an "O" since their blood already recognizes the "markers". This makes AB candidates better recipients for blood.

In addition to an individual's blood type governing the blood transfusion process, blood types may also confer resistance or susceptibility to certain bodily dysfunctions or diseases. For example, type "A" individuals may be naturally more prone to cancers of the digestive system, and individuals with type "O" are more prone to cholera, plagues, or even malaria (interestingly, they may be more prone to be preferred targets of mosquitoes, compared to the other blood types).

Overview of an original study on ADHD and blood types:
Returning to our main discussion, it appears that certain blood types may also be related to an increased likelihood of childhood ADHD or related disorders. A Chinese study recently came out which sought to investigate whether certain blood types were actually more likely to be affiliated with ADHD. The results, while preliminary, should nevertheless pique some interest on the topic among professionals.

Here are some of the major highlights of the study:

• Blood types (using the "ABO" format) were taken from 96 children and their parents, to determine the heritability patterns of blood types.
• Both ADHD and non-ADHD children were observed in the study, and their blood types were broken down.
• The study found that children who did have ADHD were more likely to have inherited either the "A" or "O" type blood from their parents.
• Conversely, children who inherited the type "B" blood (which would include either the "B" or "AB" form) were less likely to be diagnosed with ADHD.

** A caveat concerning the findings and reproducibility of this study: It is important to note that the study population was relatively small, especially for a study of this magnitude which seeks to identify general trends between blood types and their relative association with co-existing disorders. Some blood types can be relatively rare, for example, in the United States, only around 10% of the population has type "B" blood and only about 15% has the "B" in any form (types B or AB). Although blood types vary extensively all over the world, certain types tend to predominate, which requires large populations to be studies to ensure all groups are sufficiently represented. Thus, small population studies can easily produce skewed results. Nevertheless, I personally believe this study was a good starting point.

**Blogger's personal notes/opinions on these findings:

I found this study to be interesting. Unfortunately, I could not read the whole article (the majority is in Chinese!), but the possibility of blood typing being related to ADHD would be a major breakthrough, if these results are able to be consistently replicated with larger population studies.

My first thought was that maybe some nearby gene related to ADHD might be influencing the blood type/ADHD connection, but no significant genes associated with ADHD exist on the 9th chromosome (at least to the best of my knowledge after conducting a search of OMIM for the term "ADHD", a national database which ties down diseases and disorders to known genetic regions). However, genes which are located far apart from each other, even on completely different chromosomes can also work in tandem, so genetic relationships between ADHD genes and blood type genes cannot be ruled out entirely.

Another option may be some type of indirect connection between blood type and ADHD. For example, the article notes that individuals who have the "O" or "A" blood type alleles are more prone to ADHD. Other sources note that individuals with type "O" are more prone to developing intestinal and gastric ulcers, and that individuals with type "A" are more prone to cancers of the digestive system (such as cancers of the esophagus, pancreas and stomach). This may signify that these blood types (compared to those who have "B" or "AB" blood) may be more prone to digestive problems.

Digestive disorders can result in poor nutrient absorption (we have discussed nutrient deficiencies in ADHD in number of previous posts), which may leave one more prone to ADHD symptoms. Additionally, digestive dysfunctions can actually lead to an increased likelihood of developing food allergies, as potential allergens are less likely to be broken down or "chewed up" than by a properly-functioning digestive system. Furthermore, we have also explored the possibility that acid accumulation can make its way into the brain regions and have an impact on neurological symptoms including ADHD-like behaviors. This was discussed in a recent post investigating the high prevalence of ADHD in children who suffer from frequent ear infections.

While these possibilities are strictly hypothetical at the moment I firmly believe that we should further explore the possibility of specific blood types as possible underlying causes or risk factors for developing ADHD.

ADHD and Balance Impairment: Visual and Inner Ear Deficiencies

Balance dysfunctions and visual or vestibular deficiencies: Uncommon comorbids in the ADHD spectrum:

When we think of comorbid disorders to ADHD, we often envision disorders which can be diagnosed psychiatrically. Common examples such as depression, anxiety, Obsessive Compulsive Disorders (OCD), oppositional defiant disorders, and conduct disorders often come to mind. In addition, it is perhaps no surprise that learning disabilities are relatively common in children and adults with ADHD. If we do delve into physical comorbid disorders, things like Tourette's and tics may come to mind. For those skilled in the diagnosis and treatment of ADHD, even non-trivial comorbids such as bedwetting and sleep disorders may be apparent.

However, there is another impairment that often goes along with the ADHD population, especially in children. Sensory processing disorders are often seen in the ADHD population, especially in children. This includes more "physical" dysfunctions including the ability of the child to maintain balance and equilibrium. To the frustrated parent of coach of an ADHD child, this may introduce another complication with regards to sports or other activities which involve coordination and balance, such as basketball, baseball, tennis, soccer, gymnastics, musical instruments, dance, etc.

The aim of this post is to investigate and discuss impairments in balance function in children with the disorder, We will be citing and highlighting some key studies in the overlap between ADHD and balance dysfunctions (especially relating to functions derived from visual and tactile signals) and look for possible underlying causes and treatment methods:

Brain regions involved in Balance Dysfunction in the ADHD Child:

Most experts often cite specific "hot spot" regions of the brain for the ADHD patients. Among these, the prefrontal cortex part of the brain often receives the most attention. Less pronounced, however, are the studies associating the cerebellum, and their implications on ADHD. For a reference to the Prefrontal Cortex and Cerebellum brain regions, please consult the brain diagrams below:

Shown above is a human brain. The Cerebellum region, which plays a major role in governing balancing functions and may be compromised in a significant subsection of ADHD children, is shown in purple in the top picture. The area highlighted in orange in the bottom drawing roughly corresponds to the prefrontal cortex region of the brain, which plays a major role in impulse control. Deficiencies in blood flow and overall activity of this prefrontal cortex region of the brain are often seen in children (and adults) with ADHD, and may be responsible for some of the difficulties in filtering out comments and actions for appropriateness.

The inter-relationship between attention and balance/coordination: The strong association of the prefrontal cortex and cerebellum regions of the brain:

Many studies involving brain regions and ADHD often miss this connection. The relationship between these brain regions may go a long ways in explaining ADHD comorbid disorders as well, especially the more "physical" ones such as speech complications, developmental coordination disorders, etc. While perennial "hot spot" brain regions, such as the prefrontal cortex, are frequently mentioned in studies involving brain activity in ADHD, this particular brain region is actually intricately interconnected with the cerebellum (as well as another key brain region, the basal ganglia. The role of the basal ganglia in kids with ADHD has been discussed previously in other postings, but in general, the basal ganglia tell how fast a person "idles". 'Type A' personalities, such as workaholics, individuals with OCD and overly focused individuals typically have overactive basal ganglia, whereas many with ADHD often exhibit underactive basal ganglia.).

We have already mentioned that the balance-governing regions of the brain (the cerebellum) is interconnected with a key impulse-control region of the brain (the prefrontal cortex or PFC). We also mentioned that impulsivity is a characteristic of the Hyperactive-impulsive and Combined ADHD subtypes (as opposed to the more inattentive forms of the disorder). Interestingly, the prevalence of balance dysfunction cases seems to predominate in the combined subtype of ADHD (main paper as reference source). This correlation lends further credence to the hypothesis that the balance-governing and impulse-governing regions of the brain may be "co-affected" in the case of the balance-deficient, hyper-impulsive ADHD child.

Key points concerning balance related deficiencies and ADHD:

• ADHD is often associated with developmental delays. Indeed, studies highlighting a delay in cortical maturation in children with ADHD suggests that children and teens with the disorder may fall "behind the curve". By its own very nature, the vestibular system often does not fully develop until the age of 15, so immature development in this brain region may result in deficiencies in this system throughout almost the entire span of childhood in an individual with ADHD.


• Additionally, EEG and imaging studies have also demonstrated relative deficiencies in both size and activity (by measuring blood flow patterns) in various brain regions of ADHD children. These include the cerebellum and the caudate nucleus. Both are interconnected and associate with the "ADHD region" of the prefrontal cortex (PFC). This PFC region plays a major role in the impulse-control process and deficiencies in its function can result in a weak self-regulatory system of impulsive behaviors (which are hallmark characteristics of ADHD, especially in the hyperactive/impulsive and Combined subtypes).


• The cerebellum gathers input from visual, vestibular (inner ear), and somatosensory (mainly tactile senses, such as perceived through the skin and internal organs) systems. As we can imagine, a defect in one or more of these information-obtaining sensory systems, and the cerebellum (as well as the interconnected region of the PFC) may be compromised. Thus ADHD and sensory deficits may be intricately related.


• Taking this one step further, we may wish to explore the link between ADHD and sensory disorders, including processing disorders and sensory integration disorders. One thing is for sure, however: ADHD is not simply limited to deficits in the PFC!


• The vestibular system also plays a crucial role in what is known as "gaze stabilization" (i.e., stabilizing the focus on a particular fixed object when you yourself are moving). The very nature of "gazing" obviously has visual implications as well, so a deficiency in the vestibular component of gaze stabilization may also affect visual input success as well. Interestingly (an perhaps not surprisingly), visual input deficiencies are also seen at high rates in children with ADHD.
  
  This may actually serve as one of the key contributing factors as to why maintaining attention (to, say, a teacher), may be so difficult for ADHD kids, because they literally are having trouble focusing their visual attention (gaze) on their target of interest (i.e. a teacher standing up in class giving a lecture), especially if the child is already fidgeting around in their seat. In other words, there may be some inherent deficiency in this particular component of the attention span, and needs to be addressed further in the near future.

Investigating the sources of balance impairment in children with ADHD:
In order to clarify where I am coming from on this, I will highlight an extremely recent publication in the Journal of Pediatrics by Shum and Pang. This study investigated the different systems of balance in children, including somatosensory (balance governed by tactile features), visual, and vestibular (inner ear and the sense of equilibrium). They tested approximately 50 children (ages 6-12) with ADHD for balance discrepancies by isolating each of the three systems listed above to test sensory organizations of balance. A highlight of the study can be seen below:

Instruments/Methods of the study:

1. A platform which can induce a feeling of motion on a child who stands upon it (this disrupts the somatosensory component of balance, forcing the child to use their visual or vestibular functions to compensate for the somatosensory impairment).
2. Surrounding scenery which can visually give the illusion of motion. This forces the child to use their vestibular and somatosensory methods of equilibrium, as the visual sense is disrupted. Another variation of this is to have the child perform with their eyes closed.
3. A combination of the two methods above will isolate the vestibular component of balance, as both the somatosensory and visual sources of balance are now both compromised.
4. A total of six different environmental conditions were performed to isolate one or more senses of balance. The researchers noted which of the three modes of balance were most likely to be compromised in the ADHD children. The findings are highlighted below:
   

While balance-related issues can stem from visual discrepancies, somatosensory issues (i.e. the sensations of touch and pressure from the skin and even internal organs), and vestibular (inner ear) imbalances, it appears that ADHD children are most likely to suffer from visual imbalances. This is closely followed, however, by deficits in vestibular function. Somatosensory difficulties appear to occur in ADHD children as well, but the role of this system is likely to be much smaller than for the other 2.

Possible academic implications of balance dysfunction and ADHD: Does the source of an ADHD child's balance deficiency affect his or her sensory learning style? The following points are simply the result of this blogger thinking out loud. Nevertheless, these might be some good topics of future study, as balance difficulties may be useful in evaluating academic strategies.

• These findings on balance may even extend to the classroom and affect the learning environment of an ADHD child. Given the above, abnormalities in these areas may even affect a child's mode of learning and learning style. While these assertions simply remain personal hypotheses of this blogger, a child with visual discrepancies leading to balancing difficulties may also be deficient in visual perception and therefore struggle in a visual-dominated learning environment. He or she may gravitate towards a more auditory or kinesthetic style of learning.
  

• Conversely, it is also possible that vestibular-regulated balance dysfunctions, which stem from the inner ear may actually extend to a child's auditory learning capabilities. Again, this remains a hypothesis, but given the fact that severe childhood ear infections can affect both balance and hearing (as well as ADHD symptoms, see previous post on childhood ear infections and ADHD), a child with vestibular-related balance deficiencies may also have more difficulty in a predominantly auditory-based learning environment. This may spell bad news if an ADHD child's teacher engages in more auditory discussions or as the child moves up to high school and college courses where an auditory lecture is the more common form of teaching and communication.
  

• A double-whammy?: Given the fact that children with ADHD may suffer from both vestibular and visual (and even somatosensory) information processing for balance, it leads us to wonder if the child may also have learning deficits in 2 of the 3 major forms of learning (visual, auditory or kinesthetic). If this is the case, trying to accommodate an ADHD child's education could be extremely difficult, if he or she must heavily rely on only one predominant mode of acquiring and processing information.
  
  For example, if a child were to undergo a study similar to the one listed above, and it turns out that he or she is weak in both the visual and vestibular forms of balance, and (this is a big "if" and is only hypothetical at the moment) the whole balance governing/learning style hypothesis holds true, he or she may have to rely on a predominantly kinesthetic form of learning. While this child may succeed in hands-on learning subjects (i.e. frog dissection or wood shop class), he or she may have an exceedingly difficult time in other subjects such as algebra or history where hands-on-learning opportunities are more difficult to implement.
  
  

• The role of balance and sensory stimulation may have even greater-reaching academic implications. Another study just came out recently investigating the role of posture stability (i.e. how well a person stabilizes their center of balance) on ADHD and dyslexia. The study found that comorbid ADHD symptoms greatly influenced the effects of posture stability in dyslexic individuals, which may even have implications to affecting the reading environment of the individuals with dyslexia. It's important to keep in mind that this study involved adults instead of children, but the fact that ADHD may play such an integrated role into sensory modulation of other disorders into adulthood may signify the deep level of inter-relationship between cognitive function and sensory motor stimulation.
  

Vestibular Stimulation as an alternative form of ADHD Treatment?: As an interesting aside, there has been some pronounced effect on treating ADHD symptoms with a non-pharmaceutical alternative method called vestibular stimulation. We will be addressing the validity of these findings and their potential for practical usage in a later discussion.

Childhood Ear Infections and ADHD: Why the link?

When we scan the literature for statistics on ADHD and search for early warning signs or tip-offs that a young child may be prone to the disorder, a few common trends seem to pop up again and again. One of these is the high rates of ADHD and attentional difficulties in kids suffering infection of the middle ear (Otitis Media) in early childhood.

During early childhood, the actual positioning of the ear canal is still adjusting, the pathway into the middle part of the ear is actually at a flatter angle than in a mature adult. This difference in positioning actually makes younger children much more prone to ear infections than older children or adults. Unfortunately, these infections may increase the risk of further complications down the road, including an increased onset of attentional difficulties, including ADHD. Here is what some of the literature has to say about the ADHD/ear infection connections:

Relationship between middle ear infections and inattention: The basis for inattentive ADHD?

The main culprit for attentional deficits is often believed to be the result of hearing loss (even mild), early in a child's life due to complications with the middle ear, including infections, allergy-related causes or build-up of fluids in the canal. As a result, the child begins to miss out on verbal cues, and does not develop the same level of response to an adult voice. Auditory deficiencies (including auditory processing disorders) may stem from this key development period, even if the hearing difficulties are only temporary.

Not surprisingly, there is a wealth of data associated with hearing loss due to middle ear complications can lead to language processing difficulties. We have seen how auditory processing disorders can often occur as a comorbid factor in ADHD, and may be linked to seemingly unrelated behaviors including comorbid anxiety and conduct-related disorders.

It is important to note, however, that other early childhood studies have not seen a link between infection and attentional difficulties (observed by parents, teachers, or clinicians).

Interestingly, environment may play a huge role in explaining this discrepancy between study results. One study found that children who had middle ear complications early on along with poor home environments were significantly more likely to develop attentional difficulties (along the lines of what would be classified as ADHD). Therefore, the effects of early ear infections on compromised attentional difficulties may be significantly reduced if a supportive home environment is maintained for a child. This is good news for parents of children with ear infections. But what about the hyperactive component of ADHD?

The link between hyperactive behaviors and middle ear complications: The basis for hyperactive/impulsive or combined subtype ADHD?

While it seems more intuitive that ear infections could lead to auditory problems and subsequent attentional difficulties (especially to auditory cues), the relationship between ear infections and hyperactivity is less inherently obvious. This association would be more relevant to the hyperactive/impulsive and combined subtypes of ADHD.

For over 30 years, researchers have linked high rates of ear infections and hyperactivity (this study used the term "minimal brain dysfunction", a phrase which this blogger has personal objections, nevertheless, it is a relatively common term in the literature). Later studies confirmed these findings, including one which reported the majority of children medicated for hyperactivity had a past history of 10 or more childhood ear infections. These numbers were in sharp contrast to the prevalence of ADHD in non-hyperactive children.

One thought may be that ADHD which includes a significant hyperactive component (as opposed to the more inattention-dominated form of the disorder) is more likely to be associated with comorbid disorders that correspond to ear infections. We have seen previously that comorbid disorders to ADHD are often related to particular subtypes.

For example, anxiety and depressive-like symptoms are often more likely to co-exist with primarily inattentive ADHD, while conduct disorders are more likely to co-exist if there is a high hyperactive/impulsive behavior (especially in the combined subtype). In general, the prevalence of more severe learning disabilities is often more associated with the inattention-dominant form of ADHD, while motor tics are more likely to be a hyperactive/impulsive trait. Carrying these associations in mind, are the studies linking early ear infections to hyperactivity simply due to associations with hyperactive subtype-dominated comorbid disorders?

One particular study found that children with hyperactivity vs. children with learning disabilities (and not hyperactivity, remember, learning disabilities are often seen at higher rates in the inattentive forms of the disorder) had similar numbers of total childhood ear infections. However, the timing of the infections did seem to matter. Children with hyperactivity experienced more recent ear infections (within the previous year) compared to the learning disability kids.

In other words, the question surrounding hyperactivity and ear infections may be more of a "when" question than a "how many" question. This may also suggest the possibility that hyperactivity due to middle ear troubles may be more of a temporary condition (this is supported by trends as an individual with ADHD ages, typically, the hyperactive symptoms of the disorder begin to subside as a child gets older and reaches adulthood, while the inattentive symptoms are more likely to plateau) as opposed to inattentive problems stemming from ear infections. Severity of the infections may also be a triggering cause or associated warning sign of an increased risk of developing hyperactive behaviors. The same study found that earaches and upper respiratory tract infections were higher in the hyperactive group than in the less-hyper learning disability group.

So what's going on with the connection between ear infections and ADHD-like hyperactivity?:
Although none of the above studies mentioned this possibility, as a blogger I have a few ideas on the subject. One of the most probable reasons for the ear infection/hyperactivity correlation may be due to the treatment process of ear infections. Let me explain:

Ear infections are typically treated with antibiotics. While these drugs work wonders for most infections, they also can disrupt the healthy bacterial counts in the digestive tract (that is, they kill off many of the "good" bacteria in our digestive systems in addition to the "bad" bacteria which may be causing our infections).

If the "good" digestive bacterial counts fall too low, the digestive process is compromised. The absorption and digestion process may suffer, as key nutrients may now be compromised (even if no major dietary changes occur). We have spoken extensively about nutrient deficiencies and ADHD as well as ADHD-related nutrition strategies in earlier posts.

Additionally, if good bacterial counts fall low, incomplete digestion results, which can lead to byproducts such as higher concentrations of organic acids, as well as incomplete breakdowns of potential allergens (which can increase sensitivity to food allergens, among others). These allergens and acids can actually begin to penetrate the blood brain barrier and show up in higher concentrations in the brain. Neurological disorders, including abnormal hyperactivity may actually be triggered by digestive imbalances (to a degree beyond what most of us realize). We are just beginning to recognize the huge degree of inter-relationship between the nervous and digestive systems, including brain-gut interactions.

There has been a longstanding "hot" discussion surrounding food allergies and ADHD (as well as possible connections between food allergies and disorders like fibromyalgia and chronic fatigue syndrome), and the disrupted bacterial balance in the digestive system due to frequent antibiotic usage for recurrent ear infections may be a governing factor. This seems to make sense, especially considering the fact that hyperactivity was more linked to recent ear infections (and resultant antibiotic treatment), while the more inattentive behaviors and learning disorders seem to be a more long-standing symptom. Since bacterial counts begin to re-stabilize following antibiotic treatment (if a proper diet is maintained), the food-related hyperactivity may begin to subside, but for recent infections and treatments, the digestive bacteria may still be imbalanced, triggering an onset of ADHD-like hyperactive behaviors.

Of course this is just the blogger's personal hypothesis, but it at least seems plausible that the actual treatment for ear infections may play an equally strong role on the high rate of occurrence between ADHD and ear infections.

Ginkgo biloba for ADHD: A natural herbal treatment alternative?

A few weeks ago, I discussed the merits of ginseng for treating ADHD. What I did not mention is the fact that this special herb often works even better in tandem with another important "brain herb", Ginkgo biloba. It's benefits also extend beyond the nervous system, and the Ginkgo has been used to treat everything from increasing blood flow to Alzheimer's to glaucoma to hormone replacement to protection against neuronal degradation. While somewhat wary (personally) of using generalized "brain booster" nutrients for ADHD (it is a highly variable disorder of complex etiology and treatment methods), I am interested whenever new research publications arise on the topic. Just this week, a new paper came out on the merits of Ginkgo biloba as an ADHD treatment option.

Here are some of the major points of the publication:

• Irritability is an often overlooked side effect of ADHD. Medications, especially over-prescription with stimulants such as methylphenidate and amphetamines can increase this unwanted side effect. However, Ginkgo exhibited a positive mollifying effect on irritability for the individuals in the study.
  
  
• While one of the knocks against Ginkgo biloba is that it can sometimes result in sedative effects, the study found these to be extremely mild. However, to go along with the irritability-reducing benefits above, Ginkgo was able to improve the individuals' tolerance for frustration (to the degree that this behavior could be measured).
  
  
• We have seen previously that oppositional defiant behaviors are often comorbid to ADHD (which can often manifest themselves alongside seemingly unrelated disorders such as auditory processing disorders or even bedwetting). One of the strongest suits of Ginkgo biloba may actually be in curbing these oppositional behaviors. This suggests that Ginkgo may be effective for the more Hyperactive/Impulsive or Combined Subtypes of ADHD, where comorbid oppositional behaviors are more often seen (as opposed to the predominantly inattentive subtype of the Disorder).
  
  
• Nevertheless, Ginkgo biloba appeared to boost symptoms of attention and working memory as well. This may suggest Ginkgo's versatility, and that it could be used universally across the ADHD "spectrum", including for the 3 classic or traditional subtypes of the disorder.
  
  
• The study highlights the relative success for co-treatment with methylphenidate and clonidine for individuals with ADHD and comorbid anxiety disorders. The authors suggest a functional comparison between Ginkgo and clonidine, and hint at its use as an alternative to clonidine/methylphenidate treatment (of course, it is also possible that Ginkgo may be used alongside lower doses of stimulant medications, which could be very useful in reducing unwanted side effects, which are often mild for low doses of stimulants, but typically begin to appear with greater frequency when stimulant dosing is increased). Thus, Ginkgo could possibly act as a side-effect-saving alternative to higher doses of medication.
  
  
• As a precautionary measure, due, in part to some of its anti-clotting properties, there is some concern about Ginkgo triggering internal cerebral bleeding. Indeed, other studies have also addressed this possible concern, highlighting issues such as haemmorrhage risks, as well as herb-drug interactions with Ginkgo and anti-coagulant medications.
  
  
• Keep in mind the extremely small nature of the study (only 6 individuals) should be met with healthy skepticism. However, the results were still notable. Statistically significant reductions in some of the trademark ADHD symptoms (fidgeting, restlessness, inattention, etc.) upon Ginkgo biloba treatment definitely highlight its potential as a more "natural" alternative treatment method for ADHD.
  

Why the Menstrual Cycle may affect ADHD Medication Dosing Levels

Do hormonal fluctuations result in variable ADHD medication dosage levels across the menstrual cycle?

We have investigated the impact of gender on ADHD in a number of earlier posts. We have covered topics such as:

• Gender Based Metabolic Differences in ADHD brains

• Gender Dependent ADHD Genes, including MAOA, SLC6A2, SLC6A4 and COMT

• ADHD subtypes and Comorbid Disorders

Clearly, there are a number of boy/girl differences in the root causes, diagnoses and treatment methods for the disorder.

However, we need to investigate whether intra-individual differences are also an important factor, especially where medication treatment and medication dosing levels are concerned. Based on a number of studies, it appears that women may actually require different medication dosing levels depending on where they are in their menstrual cycle. Additionally, post-menopausal drugs such as estradiol patches may also alter the drug effects of certain ADHD medications such as amphetamines. The main culprits are most likely fluctuating levels of estrogen and progesterone.

Here are brief summaries on some of the relevant studies and their findings. Wherever possible, I will include a link to the original studies:

• The link between Estradiol treatment and amphetamine medications: This study focused on whether pretreatment with estradiol played any role in the reaction to amphetamines. The drug used in this study was D-Amphetamine, which would correspond to the medication Dexedrine, however, this is also the predominantly active compound in medications such as Adderall or Vyvanse (once this "pro-drug" is metabolized). It is unclear at the moment whether chemical "cousins" to amphetamines, such as methylphenidate (Ritalin, Concerta, Daytrana, Metadate), also exhibit these fluctuations when combined with estradiol-releasing drugs.
  
  The study found that for females who took estradiol-supplementing treatments during the early follicular phase (pre-ovulation) of the menstrual cycle experienced an overall greater "stimulating" effect of the amphetamine medication (taken as 10 mg of amphetamine). This may suggest that a slightly lower dosage during this stage of the menstrual cycle might be warranted, and (as this blogger's personal hypothesis) may actually affect the addiction potential of ADHD stimulant drugs such as amphetamines.
  
  
• Another study by the same group found that estrogen may be responsible for some of the heightened euphoric effect felt from amphetamine-based drugs. However, the hormone progesterone may actually counteract some of this euphoria. During the luteal phase of the menstrual cycle (after ovulation), high levels of both estrogen and progesterone are seen (although levels of both of these taper off going into menstruation), so the effects of estrogen may be curbed. During the late follicular phase, where progesterone levels are low and estrogen levels begin to spike, the "high" may be at its peak, especially if stimulants are involved.
  
  
• A case study found that an increase in inattentive symptoms coincided cyclically with the menstrual cycle for a patient who was undergoing treatment for newly-diagnosed ADHD with a twice-daily dosing regimen of the stimulant medication Concerta.
  
  
• The findings from these two studies suggest the possibility that a slightly smaller dosing schedule with amphetamine-based ADHD medications (such as Adderall, Vyvanse or Dexedrine) may be warranted during the follicular phase. However, during the luteal phase, when progesterone levels are higher, the amphetamine-based effects are less pronounced. This may correlate to a slightly higher dosing regimen for amphetamine-based treatment for ADHD and related disorders.
  
  
• While there is a relatively good theoretical basis for this assertion above, practical consideration measures must also be considered. Based on the relative scarcity of studies (besides the 2 mentioned above) on the amphetamine-menstrual cycle interactions, it is unclear as to how pronounced the medication change should be.
  
  For instance, should someone taking 10 mg of Adderall during the follicular phase boost up to 15 mg for the luteal phase? 20 mg? 30 mg? Additionally, hormonal fluctuations vary during the phases themselves, such as the estrogen spike during the late follicular phase. Questions abound, especially when dealing with the brief ovulatory phase as well.
  
  

This blog post hopefully introduces what may be a new consideration to women who have ADHD and are currently taking stimulant-based medication treatments. Perhaps this posting simply confirms what you have already experienced.

Nevertheless, given the fact that administering variable levels of medication based on cyclical patterns such as time of day (like ramping up methylphenidate concentrations via controlled release formulations to offset "acute tolerance" based effects), and the fact that individuals with ADHD may experience seasonal variations in symptoms, at least suggests, that variable dosing of medications across the near-monthly period of the menstrual cycle may prove to be beneficial treatment strategy for females with ADHD.

Long Wave Infrared Imaging: A new detection method for ADHD?

Detecting ADHD using the long-wave infrared spectrum:

I always enjoy covering new breakthroughs in the diagnosis and treatment methods in the medical field. A new study just came out which may have a number of potential applications to aid in the diagnostic process of ADHD, which I believe is worth sharing. Called Long-Wave Infrared Imaging, this method utilizes the infrared spectrum to detect biological activity (namely bloodflow patterns) via the differences in radiation emitted by these activities. The study, titled Sensitivity and Specificity of Longwave Infrared Imaging for Attention-Deficit/Hyperactivity Disorder, found that this method may be a surprisingly powerful way of separating ADHD from other related disorders, aiding in the always-difficult process of differential diagnosis.

The basics of Long-Wave Infrared Imaging:

The term "long-wave" is a relative term, of course, referring to wavelengths of approximately 10 nanometers (or only one one-hundred millionth of a meter). Differential bloodflow patterns can result in temperature differences by a full degree (Celsius), making this technology useful in tracking bloodflow disorders. A recent publication in the Journal of Medical Physics by Bagathaviappan and coworkers suggests describes how this long-wave infrared imaging can detect areas in the circulatory system where bloodflow activity is sluggish or reduced. Typically, these areas appear "cooler" on the spectrum, due to the lack of a new, replenishing blood supply.

Applications for ADHD:

A number of studies have confirmed the hypothesis that individuals with ADHD have reduced bloodflow levels marking a recuction of activity to multiple key brain regions. Additionally, while several disorders have a number of overlapping symptoms (which can make the diagnostic process more complicated, especially if multiple comorbid disorders are present), differential blood flow patterns to the brain may be able to help make these distinctions. For example, blood flow patters to the brains of ADHD and OCD (Obsessive Compulsive Disorders) can show pronounced differences, which can aid the diagnostic process between these two disorders (while ADHD and OCD are often considered to be on "opposite" ends of the spectrum with regards to neuro-chemical signaling levels, these two disorders can often exhibit similar symptoms, such as a severe impairment in the response to verbal directions. This is especially true in younger children).

This technology may even be extended to measuring or predicting which medications may work for an individual diagnosed with ADHD, based on blood flow in specific localized brain regions. Cerebral blood flow patterns may help predict the response to common ADHD drugs such as methylphenidate (Ritalin, Concerta, Metadate, Daytrana). For example, a study by Cho and coworkers found increased blood flow in at least three different brain regions for individuals who showed poor response to methylphenidate treatment compared to their peers who did show improvements under the drug.

While the medication response study was done utilizing a different type of brain imaging device known as SPECT, which utilizes gamma rays and radioactive tracers to detect brain activity in 3-dimensional patterns. While SPECT has proven to be an extremely powerful and effectively safe method of detection (the radioactive isotope used in this method is relatively non-invasive and breaks down quickly, and the gamma rays are carefully controlled), concerned parents may still have an inherent fear of the terms "radioactivity" and "gamma rays" tend to shy away from this powerful detection method on their kids.

While this blogger personally has a very high opinion about the use of SPECT as a diagnostic tool for ADHD and related disorders, it is at least worth mentioning the possibility that long-wave infrared imaging methods may be a viable alternative method in at least some of these imaging cases (SPECT technology has been around for over 30 years, but the recent advances in computational power resurrected this technology in the very recent past, similar possibilities may abound by this infrared technology, which has been around even longer).

Keep in mind that the studies utilizing this range of infrared imaging technologies for detecting and differentiation disorders such as ADHD are still relatively scarce. Nevertheless, long-wave infrared imaging appears (at least in this blogger's personal opinion) to be a powerful diagnostic tool for ADHD and related disorders in the near future.

ADHD and Seasonal Affective Disorder

ADHD and Seasonal Affective Disorder (SAD): Are they Linked?

Is it possible that ADHD is a seasonally fluctuating disorder? It sounds intriguing, but remember, for diagnostic purposes, classic ADHD symptoms such as hyperactivity, impulsiveness and inattentive behaviors (beyond the normal range of age-appropriate behavior) must persist for a set period of time (the typical cutoff is 6 months for most cases). Nevertheless, it is worth investigating whether there is any sort of seasonal pattern to the disorder. If there is, there could be far-reaching implications such as medication dosages (if diagnosed or initially treated during a "high ADHD symptom" period may result in effects of over-medication for the rest of the year, while initial dosing during a "low-tide" season of ADHD symptoms may prove inadequate in the later months).

Intuitively, we would probably assume that ADHD symptoms would be worst during the dark winter months, but is there any data to support this hypothesis? As it turns out, there may be. Here are the results of a few relevant studies on the apparent connection between ADHD and seasonal related psychological disorders:

• Seasonal Affective Disorder (SAD) symptoms overlap and co-exist at higher rates in those with ADHD: A study by Levitan and coworkers on seasonal affective symptoms in adults with ADHD found that the prevalence of seasonal affective disorders was higher in the ADHD population than in the general population. This study accounted for some of the obvious factors such as geography (someone in Seattle would be more prone to seasonal related disorders than, say, someone in San Diego).
  
  Perhaps not surprisingly, the rate of appearance of seasonal affective symptoms was higher in women with ADHD (in general, depressive-like disorders such as SAD are more common in women in general). However, other interesting comparisons were seen, such as the prevalence of seasonal affective symptoms in the inattentive subtype of ADHD (as opposed to the hyperactive/impulsive or "combined" subtypes of the disorder). While this subtype connection may be interesting, it is important to remember that comorbid depression is often seen more in the inattentive-dominant forms of ADHD than the hyperactive-impulsive forms of the disorder.
  
  
• Overlap in medication treatments for ADHD and SAD: While we should be careful not to simply lump a bunch of disorders together just because they share similar treatment methods, the relationship between SAD, ADHD and medications such as buproprion (Wellbutrin) may be worth noting. Bupropion has shown to be clinically effective in the treatment of a whole spectrum of disorders including seasonal affective disorders.
  
  Additionally, this medication has shown its far-ranging capabilities, due, in part to its success as both an anti-depressant and "pseudo-stimulant" (of course there is a heated debate among professionals as far as whether "Wellbutrin" should even be mentioned in the same sentence as "stimulant", but its unusual, and relatively unknown mode of action keep it from an exclusive anti-depressant label, at least in the classical sense).
  
  The reason I personally use the term "pseudo-stimulant" is that bupropion can function as a dopamine reuptake inhibitor (which is one of the major modes of action of several ADHD stimulant medications and is typically uncharacteristic of most anti-depressants which often predominantly target the brain chemical serotonin). This may be evidenced by bupropion's relative effectiveness in treating ADHD (please note that bupropion or Wellbutrin is still extensively used in ADHD treatment in place of a stimulant if there is some type of depressive related disorder, however, findings such as the one in this previous study seem to indicated that buproprion may be effective for treating free-standing ADHD without comorbid depression).
  
  While again, I should reiterate that similar treatment methods does not necessarily equate to similar disorders or conditions, the relative effectiveness of this medication for treating both disorders at least leaves the door open for the possibility that there exist similar underlying modes of action between ADHD and SAD.
  
  
• The connection between ADHD and circadian rhythms: While SAD, by definition is a seasonal (as opposed to daily) issue of cyclical patterns of time, it is worth mentioning that new research is being done with regards to differences in the chronological patterns in the bodies of individuals with ADHD. In other words, there may be an actual scientific explanation behind the reasons why your ADHD child likes to stay up until three in the morning on a consistent basis.
  
  There also appears to be an affiliation with daily rhythms and ADHD subtype. For example, while impulsivity is often more associated as a "morning" behavior, the inattentive subcomponent of ADHD appears to be more affiliated with the evening. This may factor into the differences in sleep patterns and prevalence of sleep disorders in ADHD children, and may even highlight the daily schedule differences between the ADHD subtypes.
  
  If the hypothesis that individuals with ADHD are at least partially predisposed to different patterns of circadian rhythms compared to the general population, it may stand to reason that these same individuals may also be more susceptible to seasonal fluctuations. Some studies confirm this possible "double" association of ADHD to both seasonal fluctuations and circadian rhythms.
  
  
• Overlapping treatment strategy of Light Therapy for ADHD and SAD?: There has been a recent surge of evidence that light therapy, when administered at the correct wavelengths, is an effective treatment for seasonal affective disorder (and often with measurable levels of success), may now be useful for treatment in the ADHD population.
  
  As an interesting aside, there may be some unusual side effects of ADHD stimulant medications with regards to light therapy. A case study of a single child noted that there may be a possible connection between methylphenidate and photophobia (photophobia referring to fear of or excessive sensitivity to the light). Of course this observation was limited to just one patient, but the correlation of the symptoms with methylphenidate treatment at least suggests the possibility that this is a possible (albeit) rare side effect of one of the most popular stimulant medications for ADHD currently on the market.
  
  Blogger's side note: it is also worth mentioning that this case report was also published by the same individual who brought us the interesting case study which became the topic of an earlier post in this blog: excessive talking as a potential side effect of methylphenidate treatment. I will refrain from making any comments or conclusions about this, but on a personal note, I actually enjoy reading about some of these unique side effect case studies of the popular drug, and wonder if this will result in an increased level of vigilance with regards to monitoring odd side effects of common ADHD stimulant medications in both clinical studies and individual prescriptions.
  
  
• Omega 3 (n-3) fatty acid deficiency: A common underlying factor for both ADHD and seasonal affective disorders? I saved what is perhaps the best explanation for last. It consistently has been shown that individuals with ADHD are often deficient in omega-3 fatty acids. We have even discussed the theory behind omega-3 fatty acid supplementation for ADHD in earlier bloggings. Now it appears that omega-3 deficiencies may disrupt circadian rhythms as well, possibly due to an impairment in melatonin production (melatonin is a hormone which is tightly associated with the sleep-wake cycle and hence has implications on the circadian rhythm patterns in a particular individual).
  
  This may suggest that omega-3 fatty acid deficiencies may either help cause, or exacerbate the severity of both ADHD and circadian rhythm impairments. Interestingly, there is some evidence that omega-3 supplementation may be beneficial in treating seasonal affective disorders as well. In fact, diets rich in omega-3's may be an underlying reason why seasonal affective disorders are relatively uncommon in Iceland, which, due to its far-northern location, experiences exceptionally long, dark winters.
  

While I admit that the evidence for the link between ADHD and Seasonal Affective Disorders is nowhere near as strong as for other ADHD comorbid issues (such as Tourette's, anxiety, conduct disorders, and learning disabilities), I still wanted to pass on some of the information out there supporting a possible link between the two disorders. Given the close associations both between depression and seasonal affective disorders, including the argument that SAD should be labeled as a specific subtype of depression, and the high rate of comorbidity between ADHD and depressive disorders, there is certainly a possibility that the magnitude of overlap between ADHD and SAD is greater than we might imagine.

Methylphenidate, Anxiety and ADHD: How do they fit together?

Effects of Comorbid Anxiety on Methylphenidate Treatment in the ADHD Child:

Medication with stimulants such as methylphenidate has consistently proven to be a popular and relatively effective mode of treatment for the ADHD child. However, questions arise regarding its side effects. In particular, the effectiveness of methylphenidate (Ritalin, Concerta, Daytrana, Metadate) can be jeopardized if the child with ADHD also has some type of comorbid disorder (such as depression, obsessive compulsive behaviors, Tourette's and a host of other common associate disorders) which may be negatively impacted by the ADHD treatment. Anxiety-related disorders are seen in up to 35% of ADHD individuals, according to some studies.

Typically, treatment is met with some type of adjunctive medication to treat the comorbid disorder (which can be quite tricky, as it introduces the problem of potential drug-drug interactions, as well as a possible impairment in the effectiveness of the ADHD treatment medication), a non-stimulant method of treatment such as Strattera (atomoxetine), or non-drug alternatives (behavior therapy, EEG, nutrition and dietary strategies, etc.). While isolated behavioral therapy has limitations for treating ADHD (especially in cases of "refractory" ADHD), it has proven to be a beneficial mode of treatment for childhood anxiety disorders.

In the case of anxiety disorders alongside ADHD, treatment with stimulant medications such as methylphenidate can also be tricky. However, recent findings seem to indicate that methylphenidate is a safe mode of treatment for ADHD with comorbid anxiety. However, a new publication notes that there may be a significant distinction between the effects of anxiety on methylphenidate's effectiveness from a behavioral standpoint vs. a cognitive standpoint. Let me explain further.

When attempting to determine whether a child should be diagnosed and treated as having ADHD, the supervising physician often gives out rating forms to both parents and teachers of the child in question. Numerical rating scales with regards to classic ADHD symptoms (i.e. impulsivity, hyperactivity, inattentiveness, etc.) comprise the majority of the rating forms, and these results are tabulated and typically used in the diagnostic process. Additionally, these rating forms are often administered after a specific period of time following treatment (with medication, nutritional therapies, counseling or ADHD coaching programs, etc.) to assess the effectiveness of these treatments.

While the level of agreement between parent and teacher rating forms is generally high, significant differences may often be seen. In other words, how a child's perceived behavior in the home may be notably different than his or her behavior in the classroom. While there are an array of possible factors and explanations for this, the presence of comorbid anxiety may be an important but often overlooked reason for this discrepancy.

In the study titled: Predicting Response of ADHD Symptoms to Methylphenidate Treatment Based on Comorbid Anxiety, the researchers found that the behavioral improvements in children with ADHD were similar regardless of whether the child also had an accompanying anxiety disorder. In other words, a notable decrease in symptoms of hyperactivity, impulsiveness and behavioral annoyances was frequently seen. Since these symptoms are often more of the obvious tell-tale signs of the disorder, it would be easy to conclude (especially from a parent's standpoint) that all is well again.

However, on the opposite side of the coin, the side dealing with the cognitive deficits of ADHD (which, not surprisingly have immense academic implications), may tell a different story. The study found that for the ADHD children without an accompanying anxiety disorder, methylphenidate treatment often contributed to vast improvements in their cognitive function (and subsequent academic achievement potential). However, if the ADHD child did have an accompanying anxiety disorder, the methylphenidate treatment was significantly less effective (and possibly even counter-effective). This may serve as a possible explanation for at least some of the variability between parent and teacher evaluations of the same ADHD child.

This leads to the question: does comorbid anxiety affect the cognitive ability-enhancing effects in all academic areas or just in some of the sub-fields of academic-related cognitive functioning?

The study investigated this by administering a Weschler Intelligence Test (WISC III) to the children and examined the effects of comorbid anxiety and methylphenidate medication on three subcomponents of the test: Coding, Arithmetic and Symbol Search. An explanation of the results in these three subcategories with regards to what they measure, possible implications of these subcategories, and the effects of anxiety and methylphenidate treatment are summarized below:

• Arithmetic: This is a timed test in which arithmetic questions are orally presented to the children and the responses are measured, assessing both speed and accuracy. Methylphenidate treatment produced a slight improvement in the ADHD children without comorbid anxiety. However, for the children with comorbid anxiety, the use of methylphenidate was ineffective (in fact, a slight decrease in performance was seen, but this was exceedingly small. It should be concluded that methylphenidate treatment had no reasonable positive effect for the ADHD children with comorbid anxiety for this particular subcategory).
  
  This should lead to an array of questions, including ones such as "does anxiety hamper one's performance in math, if one is ADHD (or even if one is not ADHD)?". Intuitively, we would expect the answer to be "yes", as evidenced by the huge number of children (and adults) who have self-reported "mathphobia". However, some well-reputed studies seem to indicate that methylphenidate treatment can actually help with mathematical abilities. Is there something else going on here?
  
  One potential explanation (not mentioned in the study) may reside in the possible presence of a third comorbid factor, such as an underlying comorbid auditory processing disorder. Auditory processing disorders are relatively common in individuals with ADHD, however, since the two disorders often exhibit symptomal overlap, comorbid auditory processing disorders are often missed in ADHD children.
  
  Interestingly, some recent evidence has come out that there may be a connection between auditory processing issues and anxiety disorders. This possible link between anxiety and auditory processing disorders has been addressed previously in another section of this blog. Note that the arithmetic subsection is administered orally in the WISC III test.
  
  If the theory that auditory processing difficulties are seen alongside anxiety disorders, it is entirely possible that the discrepancies in the ADHD with comorbid anxiety performances me be largely due to the nature of how the arithmetic portion of the test is administered. It would be interesting to see if any improvements were seen in the arithmetic scores were improved in the anxiety subgroup if the questions were presented in a written, non-auditory format.

• Coding: This section of the WISC III test measures skills involving visual-spatial coordination, speed and concentration. The individual (for those over 8 years old) is instructed to copy a line of code substituting a number for a symbol (this would involve something along the lines of writing, say, a "1" where a star is presented, "2" for a "circle", "3" for a smiley face, etc.). A high performance in this section has implications for advanced academic tasks that involve utilizing tables and formulas (think of solving chemistry problems using data from a periodic table at the top of the page, etc.).
  
  In addition, a strong visual-spatial aptitude may have implications for things such as note taking skills and the like. As a result, a strength in this area may be particularly useful in upper-level courses involving the sciences, foreign languages and anything that requires an individual to "decode" and translate new information quickly. With regards to the anxiety vs. non-anxiety ADHD groups, both showed some degree of improvement with methylphenidate treatment for this subsection.
  
  However, the non-anxiety group showed a significantly greater positive response (around twice as big of an increase in scores for this subsection following methylphenidate treatment as the comorbid anxiety group) to the methylphenidate treatment, suggesting that comorbid anxiety was a relative impediment to methylphenidate-mediated improvements in this area as well.

• Symbol search: This subsection involves picking out or identifying whether a particular symbol is present in a row of symbols. It has direct implications on one's ability to pay attention to detail as well as the ability to quickly scan through information to find what is relevant. Both the anxiety and non-anxiety groups showed slight improvements following methylphenidate treatment, however, once again, the improvements in post-methylphenidate scores were about twice as large for the non-anxiety group of ADHD children.

Of the 3 subtests, methylphenidate treatment helped the most in the coding section, had minimal effects in the symbol search section and little (for the non-anxiety group) to no or negative (for the anxiety group) effects for the arithmetic section.

Other studies have also investigated the effects of comorbid anxiety on cognitive task performance in ADHD children. By and large, it appears that memory-based tasks are the hardest hit by an accompanying anxiety disorder when methylphenidate is administered as an ADHD treatment. Other studies have confirmed this finding on anxiety disorders impeding memory enhancement via methylphenidate treatment. This seems to agree with the data on the coding section, which involves a type of working memory for the symbol deciphering process.

Based on what we have covered here, it would be reasonable to scrutinize significant differences between parent and teacher ratings and behavioral and attentive improvements for the possibility of an accompanying anxiety disorder to go along with an ADHD diagnosis in a child. While anti-anxiety medications can be useful, and co-administered with ADHD stimulant drugs under the watchful eye of a carefully trained physician, there is also evidence that

These findings suggest that comorbid anxiety can be a serious handicap to achieving cognitive and academic-related improvements in response to stimulants such as methylphenidate. However, please note that, based on the main study of our discussion on ADHD, anxiety and methylphenidate, notable behavioral improvements were seen from methylphenidate treatment in both the ADHD + anxiety and the ADHD minus anxiety groups.

The implications of this discrepancy can be noteworthy. To the parent who is only marginally involved with their child's academic progress, and is simply concerned with getting more manageable behavior out of their ADHD child, the sharp reduction of negative behavioral symptoms may lull the parent into a false sense of security that all is well on the home front. This stratified response to the methylphenidate medication may be lost to the unassuming parent.

However, it may be possible that an accompanying anxiety disorder (and maybe even an auditory processing disorder) may be lying there dormant to the oblivious parent. For the teacher, however, an improvement in classroom behavior due to medication, but a lack of improvement in academic work (especially in memory-related tasks) may be a tip-off that an undiagnosed accompanying anxiety disorder may be in place in this ADHD child. Thus this discrepancy in medication-derived improvements may actually serve as a potentially powerful diagnostic tool for detecting an accompanying anxiety disorder in a child being treated for ADHD.