Friday, October 31, 2008

ADHD medications protect against drug abuse

There is often a heated debate amongst professionals, families and individuals surrounding the safety of ADHD stimulant medications and their potential for abuse. One camp claims that exposing the brain to amphetamines or amphetamine-like substances (drug categories in which almost every ADHD stimulant medication falls) fosters a long-term dependance and subsequent drug addiction later in life. The other side claims that these medications are safe and that by not taking them, most individuals with ADHD will attempt to "self-medicate" with illegal drugs, nicotine or alcohol. So which side is correct?

While arguments and information support both sides of the issue, it appears that, as of now, the overall safety and efficacy of stimulant medications for ADHD is relatively high. In an earlier post, we discussed the overall safety and addiction potential of Ritalin for treating ADHD. It appears that amidst the hype, the overall potential for addiction with this drug is relatively low. This is not to say that there is no risk at all, the discussion suggested that individuals with ADHD are able to handle the stimulant drug with less of a risk for abuse than those without the disorder.

Nevertheless, this was but one study on ADHD drugs and abuse potential, so I have decided to review additional articles on the topic. Based on an evaluation done by Joseph Biederman, and published in the Journal of Clinical Psychiatry, on the topic of ADHD medications and substance abuse, it appears that taking proper medications for ADHD at the correct dose results in a reduced risk of having a drug addiction later in life.

Some key findings of this study include:

  • A high percentage of previous studies on ADHD and drug abuse fail to take into account the factor of conduct disorders, which often occur alongside (but are not directly connected to) ADHD. Individuals with conduct disorders are more prone to abuse of stimulants and other drugs. Because of this, a number of these studies incorrectly label ADHD individuals on medication for having higher rates of substance abuse, when in fact, it is often the co-occuring conduct disorder.

  • Along the same lines, instead of viewing ADHD as one disorder, it is more accurate to see it as a mosaic, occuring in multiple different forms and with multiple different side effects and overlapping related disorders. For example, issues such as depression, bipolar disorders, behavioral issues and learning disabilities, one or more of which often occur alongside ADHD all become influencing factors in areas such as substance abuse. Failure to allocate a "correction factor" for these co-existing and overlapping disorders unfairly puts the blame on ADHD and results in an inaccurately high level of negative effects being placed on the disorder.

  • For studies which did factor out these co-existing conditions, it was determined that childhood ADHD by itself does increase both the potential for and earlier onset of substance abuse, by two-fold. The duration of abuse was also longer, and typically followed individuals into adulthood. Therefore, both ADHD, as well as symptoms which commonly occur alongside it can each, independently as well as in conjunction, increase the risk of future persistent substance abuse.

  • The article referred to a large study done previously (by the same author, which included a 4-year follow-up for test subjects), which observed that siblings of ADHD children were much more likely to have substance abuse issues than the ADHD children themselves (around 4 times greater). Adults with ADHD were higher than either the ADHD children or their siblings.

  • While unmedicated children with ADHD made up only 25% of the test subjects in the 4-year study listed above, they made up 75% of the substance abuse disorder cases. This was true not just for amphetamines (which are chemically similar to most ADHD stimulant medications), but also other drugs such as marijuana, cocaine, hallucinogens and alcohol.

  • The article concluded that proper medication for ADHD in individuals (with a focus on males in their mid to late teens and early 20's) resulted in a significant reduction in later substance-abuse risk.

Based on these findings, we should strongly challenge the assumption that ADHD medications promote stimulant (or other types of chemical) abuse in individuals. Nevertheless, we should still be aware of some potential safety risks for ADHD medications.

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Sunday, October 26, 2008

The Effectiveness of Adderall as an ADHD Medication

Adderall as an ADHD stimulant medication

Adderall is one of the most popular (and currently one of the most "trendy") types of ADHD medication. As a stimulant drug, Adderall is chemically and functionally similar to other ADHD stimulants including Ritalin, Dexedrine, Concerta or Focalin. However, while most of these medications contain either one or two compounds, Adderall technically contains eight. It is a combination of four different types of amphetamines (in the salt form) and their chemical "mirror images".

A bit of a side note on "mirror images" and drug chemistry: For reference sake, consider your left and right hands. They are identical in structure, but mirror images of each other. This mirror image effect plays an important role in pharmacology, and separation of the two mirror images can be extremely important. For example, one mirror image of the pregancy drug Thalidomide was used to treat morning sickness, while the other mirror image was linked to birth defects. Fortunately this grave difference between mirror images is not seen with ADHD stimulant medications. Some ADHD drugs, such as Dexedrine or Focalin only have the "right hand" form, which have different (and often more potent) properties than the "left hand" form. Nevertheless, both mirror images of each of the 4 different amphetamines are seen in Adderall, making it a combination of 8 distinct compounds.

Returning to the main topic, this post will be focusing on the overall effectiveness of the ADHD stimulant Adderall. This information comes from a large review done in 2002 in the Journal of Attention Disorders by Faraone and Biederman. A short synopsis of the orignal article on the medication Adderall and ADHD can be seen here. Please note that these studies focused primarily on the effectiveness of Adderall vs. a placebo and not Adderall vs. other ADHD medications. There actually are studies out there comparing stimulant medications for ADHD, which will be covered soon in later posts.

Also, the form of Adderall used for this review was the standard release version. No slower/extended release (Adderall XR) analyses were covered. Given the time of this publication, Adderall XR data was still scarce. Since 2002, this has changed, and additional insight will be covered in future posts. For now, I will be highlighting some of the main findings of the article below:

  • Adderall outperformed the placebo in a statistically significant manner for both academic and behavioral improvements. These improvements were seen by all three monitoring groups: parents, teachers and clinicians, and were consistent, even among the several different ADHD rating systems used by the three groups.
  • Additionally, consistency was seen with regards to the effectiveness of Adderall regardless of whether the stimulant medication was administered via fixed-dose (a set dosage for test subjects) or via "best-dose" (the dosing was tailored to the individual by considering the size and gender of the individual, history of other medications taken and the responsiveness to these medications). This suggests the possibility that Adderall may have a more flexible range of effective dosing than most other ADHD drugs.
  • The study identified that there is often an inherent clinical bias in reporting the effectiveness of medications because "success" stories in which ADHD medications are effective are naturally published more often than for "failed" studies. A correctional factor (described in the article) was used to counteract this implicit effectiveness bias. Just keep in mind that published results are often not a full representation of data from the full spectrum of studies.
  • Adderall treatment (at various doses) appears to be almost as effective in treating aggressive behaviors as in treating ADHD. This spells good news for individuals with ADHD who also exhibit potentially violent or overly-aggressive behavior.
  • Although parents, teacher and clinicians all saw improvements with regards to ADHD across the board, the highest levels of measured improvement was typically seen by those in the medical profession. Parent and teacher evaluations showed similar levels of improvements with respect to each other, but their results were often not as pronounced as those done by clinicians.
  • In addition to clinician reports giving higher ratings, the mode of measurement for ADHD symptom improvement was also a factor. Symptom ratings scales, refer to a reduction in negative symptoms associated with the disorder. They do not take into effect things such as improvements in school or improvements in social skills, as these are more difficult to monitor as measurable "symptoms".
  • By contrast, global ratings also incorporate factors in addition to the symptom ratings. In addition to measuring levels of "sickness" like symptom ratings, global ratings measure more degrees of "wellness", such as the social or academic improvements mentioned above. As a result, global ratings typically offer a wider spectrum and offer a more complete and detailed portrait of improvements following modes of treatment for ADHD. Not surprisingly, due additional improvement categories which can be measured, global ratings typically result in higher rating scores of medication effectiveness than do ADHD symptom studies.
  • Based on the layout and distribution of the data, and the overall high level of agreement in the results of multiple unrelated studies, the authors of the article concluded that additional studies on the topic of Adderall medication vs. placebo are unlikely to refute these results.

These results support the idea that ADHD treatments with Adderall are statistically superior to controls (i.e., it is highly unlikely that improvements along the spectrum of undesirable behaviors and effects of ADHD are due to the "placebo effect"). As a result, it is apparent that Adderall has solidified its place as a valid and viable treatment option for ADHD.

Nevertheless, we must now begin to focus on the overall safety of this ADHD drug, and how Adderall stacks up against other ADHD stimulant medications such as Ritalin, Focalin, Concerta, or Dexedrine. Please check for more posts addressing these two key areas in the near future.

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Saturday, October 25, 2008

Do ADHD Stimulant Medications Worsen Tourette's and Tic Disorders?

Main Categories: ADHD Stimulant Medications and Comorbid Disorders

In an earlier post, I commented on how Atomoxetine (Strattera) was a good possible medication option for treating ADHD comorbid with Tourette's Syndrome. One of the reasons I gave was that ADHD stimulant medications have been linked to worsening Tourette's cases and tic disorders. But how much of a link is there really between these disorders (which frequently are seen alongside each other, that is they are comorbid disorders).

I examined a review article from a couple years ago recently, and I think that it made some interesting points. Additionally, it did a very thorough investigation on the topic of ADHD, Tourette's and tic disorders, covering a number of previous experiments and journal articles. This review article was from the 2006 journal of Seminars in Pediatric Neurology, researched by G. Erenberg. A link summarizing some major points of this article on Tourette's, ADHD and Stimulant Medications may be found here. I will summarize some other important findings of this article below:

  • ADHD has been seen in up to 90% of children with Tourette's, with studies post-1980 studies showing higher percentages that pre-1980 ones
  • Although the two disorders are often seen alongside each other, the "form" of ADHD seen alongside Tourette's is the same as the form of ADHD seen without Tourette's
  • Increases in the frequency or severity of "tic" disorders (twitching, eye-blinking, etc., and occasional vocal outbursts) have been seen in a number of individuals following treatment with ADHD stimulant medications, but at the population level, these symptoms increases are typically insignificant.
  • After 1995, studies with Tourette's often separated out samples with ADHD and those without ADHD. For studies before 1995, this was often not the case. Therefore, studies after 1995 comparing Tourette's, ADHD and combinations of the two are often preferred when studying the two disorders.
  • A pre-1995 study (1992), concluded that individuals with Tourette's along with Obsessive Compulsive symptoms had worse attention span, while a post-1995 study (1998) showed that individuals with ADHD and individuals with a combination of ADHD and Tourette's had a worse attention ability than those with only Tourette's. Again, this may have been due to the later addition of the "post-1995 ADHD + Tourette's" subcategory.
  • Tourette's Syndrome (TS) is typically not associated with learning disabilities by itself, while ADHD and ADHD with TS are.
  • For individuals with Tourette's, ADHD can make tics worse. Additionally, ADHD boosts levels of rage, anxiety, delinquencies and oppositional tendencies in indviduals with TS (i.e., for those with both symptoms, the ADHD is thought to be the one at work for these negative side effects).
  • For individuals with Tourette's, aggressive behavior is often not an issue, but if it is accompanied by either ADHD or OCD (Obsessive Compulsive Disorder), aggression is often seen at noticeably higher levels.
  • The effectiveness of stimulant medcations for ADHD is typically unaffected by whether the individual also has accompanying TS.
  • The Physicians Desk Reference (PDR) includes a warning on individuals with tics (or a parent or sibling with tics) to avoid stimulant medications. This decision was influenced in part by a pre-1995 (1983) study linking ADHD stimulants to the development of tics.
  • "Questionable" ADHD stimulant drugs that allegedly boost tic disorders include: Methylphenidate (Ritalin, Concerta, Focalin), Dextropamphetamine (Dexedrine), and Pemoline (Cyclert).
  • If an individual has a current or pre-existing condition of tics, then the influence of ADHD stimulant drugs on this tics has produced a host of mixed results.
  • Within individuals who have Tourette's Syndrome, tic symptoms are often slow to appear (i.e. it take months or even years for individuals with Tourette's to see tic disorders set in).
  • For individuals who take ADHD stimulants and develop tics, the timeframe between starting the medication and developing tics is often relatively long (several months to 1 year, as opposed to immediately). Therefore, if tics show up within a short time-frame in and individual after taking stimulants (less than a month), there is significant possibility that the cause of the tics is medication-related.
  • A small sample study demonstrated that methylphenidate (Ritalin, Concerta) was less likely to promote tics than dextroamphetamine (Dexedrine).
  • Methylphenidate was shown to be "tic-safe" when combined with another anti-hypertensive agent also used as a non-stimulant medication used for ADHD (clonidine).
  • Additionally, minimal research has been done to see whether "anti-tic" medications such as Risperidone or Guanfacine (Tenex) are more or less effective for so-called stimulant-induced tics vs. "natural" tics.

I know I have made a number of "points" summarizing Dr. Erenberg's article on stimulant ADHD medications and tic disorders. However, even if you've skipped down to this point, it seems that based on the research that is currently out there and what we have so far, taking ADHD stimulant medications is relatively safe, even if an individual has Tourette's. Although there is a warning in the Physician's Desk Reference about psycho-stimulant medications worsening tics, the overall effects are relatively small, especially when compared to other disorders that sometimes occur alongside ADHD (such as ADHD and eplilepsy).

Please keep in mind, it is not my intention to try to override this PDR warning or your physician's choice of prescriptions! However, if you are currently diagnosed with ADHD and Tourette's and are on a stimulant medication, please don't run to change your prescription. From the evidence we have currently seen, it appears that ADHD stimulants, especially methylphenidate (currently thought to be one of the safest stimulant medications for ADHD) are still thought to be relatively safe, even for Tourette's. However, keep in mind that if tic disorders are not seen prior to medication, and show up within a month or less, there is a good chance that the ADHD stimulant you were prescribed is to blame. If it is significantly longer (i.e. several months or years), chances are the tics are probably unrelated to the medication. I will continue to investigate these connections and keep on the lookout for more useful articles on the subject matter of ADHD, Tourette's and tic disorders.

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Thursday, October 23, 2008

How Addictive is Ritalin?

ADHD Medications

The controversy and discussion surrounding the safety of medications for ADD and ADHD is nothing new. Among the most common criticisms of these drugs are concerns about their abuse potential and their potential risks of being habit-forming drugs. Methylphenidate (the generic name for Ritalin and Concerta), has often been mentioned in the same sentence as "cocaine", especially among the "anti-medication" and "alternative treatment" sites for ADHD treatment options. While some of these comparisons are definitely warranted, the chemical structures and modes of action of ADHD stimulants such as amphetamines and the amphetamine-like methylphenidate and the illegal street drug cocaine do bear some striking resemblances. However, it is important that we do not get lost in the hype surrounding these relationships, and instead immerse ourselves in only the facts.

In the field of organic chemistry, even minor alterations to a drug's molecular makeup can result in significant functional differences. With this in mind, however, investigation into the abuse potential of stimulant ADHD medications such as Ritalin, Concerta, Daytrana, Adderall, Dexedrine, and Focalin should be carried out in a thorough, unbiased manner. A review article from the Journal of Clinical Psychiatry on the abuse potential of the ADHD drug methylphenidate investigated key properties of the drug that play a major role in abuse potential (such as drug absorption, products produced when the drug is metabolized, and how fast the drug clears from the body). Some key findings of the article on this popular stimulant medication are summarized below:

  1. When injected, methylphenidate, cocaine, and d-amphetamine all produced similar reinforcing effects in human subjects (keep in mind that injections produce drug effects that occur much faster than those taken orally in almost all cases)
  2. Sleep deprivation boosted the reinforcing effects of methylphenidate.
  3. Methylphenidate displayed similar abuse potential to d-amphetamine for a number of studies of the general population (read "non-ADHD" population).
  4. PET scans of the brain following methylphenidate and cocaine (when both were injected) showed similar absorption rates and binding levels to their target (called the Dopamine Transporter Protein or DAT. For more more info on the DAT and ADHD, please click here). However, methylphenidate was cleared much more slowly than cocaine, which correlates to a significantly lower addiction potential for the popular ADHD drug. A quick note about this: The faster a drug is absorbed in the brain, the greater the "high" is, typically. Since injections and snorting both get the drug into the system faster than when taken orally, these methods typically lead to much greater highs and addiction potentials. Additionally, the faster this drug is then cleared, the more it is "missed" by the brain, which also results in a greater addiction potential. So for a fast-acting and fast-clearing drug, the addiction potential is typically very high. For comparison sake, methylphenidate takes about 10 minutes to enter the brain when injected (for cocaine, it is about 5 minutes), and then takes about 90 minutes to clear halfway (for cocaine it is around 20 minutes). Thus, due to its slower uptake and even slower clearance rate, methylphenidate runs a much lower risk of being habit-forming than cocaine.
  5. Oral administration of methylphenidate is much slower than this, often taking at least 1-2 hours to peak in concentration in the brain. Extended and slow-release versions of the drug (Concerta, Ritalin-SR) reduce the abuse potential even further.
  6. Individuals with ADHD are thought to have a higher amount of binding sites (DAT, see point #4) for these stimulant medications than do those without ADHD. According to the author, this makes individuals with ADHD less susceptible than the general population to habit-forming addictions surrounding the use of the stimulant methylphenidate. A more detailed explanation for this is given below:

Further explanation for Item #6 above: Although neuroscientists still disagree over the mechanism of action of both medicated and illegal stimulants, it is believed that when this DAT protein is "plugged up" or "blocked" by these stimulants, it cannot shuttle free amounts of the brain chemical dopamine into the surrounding cells. As a result, the levels of free dopamine between neuronal cells builds up. Since dopamine plays a key role in the "reward" process, it can also play a major role in both "highs" and "addictions" (both of which seek out these "rewards").

If individuals with ADHD have more of these transporter proteins to begin with, they are less likely to oversaturate all of these transporters. As a result, they are less susceptible to this dopamine buildup and the highs and addiction potentials that go along with it. In other words, individuals with ADHD can often accommodate higher levels of stimulant medications such as methylphenidate, making them less susceptible to addiction-level effects.

Based on this article and a number of other sources I have either read or followed, here is my overall take on the topic of addictions to ADHD stimulant medications:

I earnestly believe that when properly diagnosed, properly monitored by a competent physician or related professional, and by proper compliance by the medicated individual, ADHD medications are relatively safe, and the risk of developing an addiction a medication such as methylphenidate is relatively low.

Of course, as we've seen above, individuals who are not diagnosed with ADHD and take methylphenidate for recreational purposes, the potential habit-forming effects of the drug can at least approach the levels of cocaine or amphetamines. Keep in mind that the right medication at the wrong dosage can easily be just as (or even more) damaging than having the wrong medication.

Yes, stimulant drugs prescribed for ADHD are often closely related to cocaine in both chemical structure and mode of function, but the small differences between the two are sufficient enough to form a "safety barrier". Given the fact that so many undiagnosed individuals with ADHD or other related disorders often tend to "self-medicate", the dangers of "un-treatment" are just as real and just as hazardous. Keep in mind that "self-medication" is, by nature, a much more erratic form of treatment and typically abounds in negative side effects.

This is not to say that non-medication treatments should never be explored or considered as viable options for treating ADHD. Many of the so-called "alternative treatments for ADHD" are surprisingly well-grounded and increasingly-researched. However, I remain highly skeptical to those who claim that all cases of ADHD can be handled exclusively and completely by natural means. Natural remedies can be very effective for numerous cases involving ADHD, but their scope and range of applications are somewhat limited.

Please check back later for future posts related to many of these important topics on ADHD!

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Tuesday, October 21, 2008

Are ADHD Stimulant Drugs Bad for your Heart?

Given the rapid rise in prescription stimulant medications for ADHD, potential concerns surrounding the side effects of these medications has been a hot topic of recent interest. News alerts like to mention the potential dangers of these drugs, and "natural health" websites are often even quicker to point out these flaws (often to the point of exaggeration).

While it is a medical fact that stimulant medications do carry certain health risks, I believe that the big question we should be asking ourselves surrounding this issue is not whether amphetamine or amphetamine-like medications are dangerous for us, but rather how can we minimize these negative effects of these substances and keep their usage as safe as possible? After all, untreated ADHD can cause enough problems in and of itself (I will describe some of these lesser known consequences in a later post).

There was a relatively recent article (2006) in the New England Journal of Medicine titled ADHD Drugs and Cardiovascular Risk sought to investigate the overall safety of these stimulant medications for treating ADHD. This article was in the Perspective section of the journal, meaning that this was an opinionated piece. We should always be careful about drawing conclusions based on opinionated sources, but I believe that the author, Steven E. Nissen of the Cardiovascular Medicine division of the Cleveland Clinic and member of the FDA Advisory Committee on ADHD drugs, makes some very important points that are at least worth mentioning.

Some of the key points of the article are summarized as follows:
  • The administration of mixed amphetamines (Adderall) and the amphetamine-like compound methylphenidate (Ritalin, Concerta) both raised systolic blood pressure (the higher number) by about 5 mm Hg. Based on other reviews, elevated blood pressure, even of this magnitude can pose as a major cardiovascular threat.
  • Taking medications of this class (called sympathomimetic agents) results in a long-term increase in heart rate at potentially dangerous levels.

  • Several drugs which are chemically similar to ADHD stimulant medications have been either pulled from the market or are subject to strong medical lobbying efforts for removal. Drugs such as ephedra and phenylpropanolamine (PPA) are both chemically similar to ADHD stimulants and have similar overlapping modes of action. Ephedra has been linked to the deaths of several professional and amateur athletes and a warning has been issued surrounding PPA and increased risks of hemorrhaging and stroke.
  • The Adverse Event Reporting System (AERS), which is a database used by the FDA to detect potential risks surrounding medications and other treatments, turned up multiple reports of sudden deaths associated with ADHD stimulant drugs, several which involved individuals with pre-existing cardiovascular defects and conditions. Additionally, a significant number of non-fatal heart difficulties such as heart attacks, irregular heart beats and stroke were observed.

  • Many of these reports were "without proper documentation", so the FDA could not make any definitive conclusions from this data. Based on this blogger's opinion, the phrase "without proper documentation" could refer to either data which is not complete to the point of being statistically significant to warrant further action, or information that was disregarded due to minor "technicalities" intrinsic to a bureacratic system. It is neither my place nor my intention to villainize the FDA, but it is important to at least consider this information and keep it tucked away in the backs of our heads.

If the information and conclusions of the article appear bleak to you, that is because they are. Nevertheless, it is important to note that this is one person's opinion, which, although echoed by many, is by no means unanimous. Having said that, I believe that the following steps should be taken for anyone considering stimulant medications for ADHD or a related disorder:

  1. A thorough screen of both an individual's background and their family history should be done before starting any type of ADHD stimulant medication.
  2. Numerical measurements such as blood pressure and heart rates should be taken frequently and passed on to the individual's physician. Keep in mind that even moderate increases in either of these can pose serious cardiovascular risks over time.
  3. For individuals with pre-existing heart problems, these medications should only be taken in cases of severe levels of ADHD (where the risks of non-treatment would be potentially more injurious to the individual than the elevated cardiovascular risks associated with these drugs).
  4. Even minor changes and symptoms need to be reported immediately and communicated to a supervising physician.

I believe that, in spite of the information presented in this, as well as other articles, ADHD medications can still be administered safely. However, I also believe that a more stringent set of conditions should be met, especially with regards to an individual's overall cardiovascular health. For those who believe that they fall into the "cardiovascular risk" category, I will soon be outlining some useful strategies to help reduce the potential risks and improve the overall safety of these ADHD medications.

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Saturday, October 18, 2008

ADHD Medication Recall: Dextroamphetamine Sulfate

ADHD Medications

While far from catastrophic, it is worth mentioning that there was a recent recall by some manufacturers of the ADHD stimulant medication Dextroamphetamine Sulfate. Dextroamphetamine, which also goes by the trade name Dexedrine or Dextrostat (by other manufacturers), is a relatively potent stimulant used to treat ADHD and anxiety disorders. ETHEX issued a release to the FDA on Tuesday October 15, 2008 about a recall of the 5 mg tablets of its version of the drug. Tests had shown that a sample of the medication contained oversized tablets that included a noticeably higher dosage than labeled (up to twice as high in some cases).

The good news surrounding this release is that no wholesalers or retailers of the drug have filed reports citing oversized tablets of the 5 mg of the drug (click here for a pictured link to this product). Additionally, the company manufactures 10 mg tablets of the same product, so even an accidental "double dose" (10 mg) of the medication does not exceed the dosing maximum for this particular product line. The frequency of negative side effects is often limited when total dosing is below 15 mg, and the drug typically does not result in severe reactions until around 30 mg (three times the "double dose") is taken.

Hypothetically speaking, an accidental overdose of Dextroamphetamine sulfate could cause an array of symptoms and side effects including an increased heart rate (tachycardia) and elevated blood pressure (hypertension). The risk is increased if antidepressants of the Monoamine Oxidase Inhibitor family (such as Selegiline, Zelapar capsules or transdermal Emsam patches) have been used within two weeks of the dextroamphetamine sulfate medications.

Aside from possible risks for those with current cardiovascular disorders, it is unlikely that any major side effects would occur from taking the occasional oversized capsule. Nevertheless, it raises the concern about medication dosing and how important knowledge regarding the dose-dependant effects of ADHD medications truly are. In a future post, we will explore how different doses of the same medication can often result in vastly different responses in a patient.

ADHD medications

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Friday, October 17, 2008

Risperidone Boosts ADHD Stimulant Medication Effects

ADHD Medications

We often search the fine print for ADHD medication labels to see if there are potentially negative drug-drug interactions. However, an equally valid question may be: are there other medications which may boost or augment the effectiveness of an ADHD medication while keeping negative side effects to a minimum? The answer to this question appears to be "yes". We have seen in a previous post how ADHD medications and treatments can often overlap those of co-occurring disorders, such as in bedwetting. We have also seen how Atomoxetine (Strattera) can be an effective treatment option for ADHD and Tourette's. We have also explored the relative safety of ADHD stimulant medications taken during pregnancy. Now we will discuss is which medication strategies are effective for ADHD and comorbid conduct disorders and evaluate the relative safety of these medication combos.

The drug Risperidone (also referred to as Risperdal or Rispen), is a relatively new antipsychotic medication which was released in 1993 for adults and was approved in 2007 as a treatment option for both pediatric schizophrenia and pediatric bipolar disorders. A year prior to this, it was used as a potential treatment medication for pediatric autism. Given the fact that individuals with ADHD are more prone to exhibiting multiple symptoms of these disorders, Risperidone is a potential agent of interest for certain forms of ADHD.

A key study was done in 2004 by MG Aman and colleagues and was published in the Journal of Child and Adolescent Psychopharmacology, which focused on the effects of Risperidone when used in conjunction with other stimulant medications for treating ADHD in children of sub-average IQ's during a 6-week study period. Additionally, differences in behavioral disorders frequently seen alongside ADHD, such as Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) were also monitored by the study.

Although not a stimulant medication itself, the study's findings suggest that Risperidone may prove to be useful in augmenting these stimulant medications' effectiveness for these disorders or combinations of disorders. Additionally, results from the study suggest that Risperidone,by itself is often an effective treatment for hyperactivity and conduct disorders that often occur alongside ADHD. When combined with stimulants, the overall effectiveness is even greater.

Safety-wise, the study found that the use of Risperidone produced no noticeable change in the number of stimulant-related adverse drug effects. The three main ADHD stimulant medications used in the study were Methylphenidate, Pemoline, and Dextroamphetamine, with levels for each medication covering a wide dosage range. It is first important to note that while methylphenidate and dextroamphetamine are both considered to be relatively safe stimulant medications for treating ADHD, Pemoline (Cyclert) is known to be potentially harmful to the liver, and is typically used sparingly, often as a last resort among many physicians. What the study observed, however, is that risperidone, when taken alongside these stimulant medications, does not increase the number or severity of these side effects (Risperidone treatment did result in slightly more weight gain than the placebo controls, but the overall difference was small). This should be taken as good news for those concerned with the overall safety and effectiveness of combining stimulant and non-stimulant medications.

While ADHD stimulant medications and antipsychotic agents have different modes of action and different biological "targets", the results of this study suggest that the two types of medication are often able to work together and improve each other's effectiveness, while incurring minimal side effects. This suggests that for children with both ADHD and some type of oppositional or conduct disorder, prescribing Risperidone along with a stimulant medication such as Ritalin, Concerta or Dexedrine may be a highly effective and relatively safe treatment option.

ADHD medications

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ADHD and Bedwetting

It's a classic problem that often puzzles parents of ADHD children. Why does my 13 year old still wet his bed? As it turns out, bed wetting, or enuresis, is a surprisingly common comorbid (co-occurring) disorder to ADHD. Other ADHD comorbid disorders that have been mentioned in previous posts include epilepsy and Tourette's Syndrome.

While there is some evidence that the two disorders share a common underlying cause (the lack of inhibitory behavior present in ADHD could span to poor muscle control), it is interesting to note that the comorbid disorder of bed wetting is connected most strongly to the Inattentive Subtype of ADHD (as opposed to the Hyperactive/Impulsive Subtype or the Combined Subtype).

Furthermore, the use of the tricyclic antidepressant drug Tofranil (Imipramine), which is often used to treat bladder control problems, has also been shown to be an effective medication for treating ADHD in some cases. We will explore this in a bit more detail in a later post, but it is important to remember that enuresis is an unusually common disorder in individuals with ADHD, especially with the Inattentive Subtype in particular. Given the fact that medications used to treat this co-occurring disorder are also sometimes useful in treating ADHD, it is my hope that other existing drugs may be further explored for their role in treating ADHD.

ADHD Medications

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Thursday, October 16, 2008

Do ADHD Medications Cause Birth Defects?

ADHD Medications and Pregnancy

Due to the impulsive tendencies of adults with ADHD (currently thought to be as high as 4% of the general adult population), one would expect higher rates of unplanned pregnancies among this subgroup of the adult population. This is, in fact, often the case. As a result, it is worth investigating whether women with ADHD, who are often on medications are posing hazardous risks to their babies by taking these drugs during pregnancy. Although this area of ADHD medications and birth defects has not been studied extensively, here are some following observations and guidelines to go by:

Since some of the most common primary forms of ADHD medications are amphetamine-based stimulant drugs (such as Adderall), it is necessary to mention the fact that amphetamine usage during pregnancy has been shown to correlate with a reduction in birth weights of these children. However, other factors of growth, such as head size or birth length were unchanged, and the birth weight reduction amounts were often significantly less than a pound compared to newborns of non-users of amphetamines (or less than a 5% difference on average). Another relatively large study done primarily on the stimulant dextroamphetamine (Dexedrine), showed no significant difference in birth weights or the prevalence of birth defects.

For medications such as methylphenidate (Ritalin, Concerta), which is not an amphetamine but rather and amphetamine-like stimulant, no significant evidence has shown any connection to birth defects or lower birth weights. However, one study in which the mothers had taken methylphenidate alongside alcohol, cigarettes and other drugs showed higher rates of birth defects, mental impairments and reductions in birth sizes. However, this study had no adequate group of controls, so the effects of the ADHD drug itself could not be determined. Nevertheless, we must leave room for the possibility that this type of stimulant may worsen birth defects triggered by other maternal patterns of substance abuse.

Some other ADHD medications have not been explored in depth in human mothers, but have been investigated in other mammals. For example, in a study done on the non-stimulant ADHD medication Atomoxetine (Strattera) in pregnant rats, it was shown that weight reduction, impaired bone development, and lower offspring survival rates were tied to high levels of this drug. Of course, this was done on a different mammalian system at doses up to 30 times higher than the recommended optimal levels for humans (on a pound-for-pound basis). An even higher relative dose done on rabbits was shown to interfere with development of the circulatory system with the offspring. However, these levels were shown to be significantly over the relative toxic level of the drug in humans.

As a quick side note, I should mention that a small fraction of the population carries an uncommon form of the genetic region CYP 2D6, which, among other things, is connected to the metabolism or breakdown of the Atomoxetine drug. Individuals with this rare form (which can be determined by genetic screens), may be somewhat more at risk than their counterparts. However, individuals with this genetic form would often exhibit adverse effects to the medication early on, and would likely be placed on a different medicated treatment option.

Based on the overall dearth of information involving ADHD medications and pregnancy, we cannot arrive at any definite conclusions about their relative safety in pregnant or nursing mothers. However, if the connection between these medications and birth defects was significant, the results of some of the aforementioned studies would likely have been much more foreboding. As a result, the use of controlled and prescribed medications at appropriate doses are unlikely to pose any sort of major threat in pregnant or nursing mothers. Nevertheless, certain drugs, although much less common as primary modes of treatment for ADHD can be utilized if potential pregnancy or birth defects are a concern.

Medications such as Bupropion (Wellbutrin), have been shown to be useful in treating some forms of ADHD and may be especially effective for individuals who also suffer from depression or those who want to quit smoking. Unfortunately, one of the negative side effects of this medication is that it can increase the risk of seizures (for more information on ADHD and seizures, please check out this earlier post). Nevertheless, aside from some of these potential risks, it appears that Bupropion poses a noticeably smaller role than most stimulants in triggering birth defects.

Additionally, the drug Clonidine, which has shown to be effective in treating ADHD in several cases (especially those cases in which an ADHD comorbid disorder such as Tourette's Syndrome), is also less likely to cause birth defects than stimulants. Clonidine, which also goes by the brand names Catapres and Dixarit, is also used as a treatment for hypertension and can also be used in conjunction with stimulant medications to treat ADHD individuals. This is often done because of the sedative effects of the drug, which, when administered strategically before bedtime, can help calm things down a bit by offsetting the stimulant effects of other ADHD medications. One major caveat with Clonidine, however, is that sudden withdrawal or discontinuation of the drug can cause a rapid and dangerous spike in blood pressure. If Clonidine is to be discontinued, the individual must be gradually weaned off the drug to avoid these negative and harmful side effects.

It is my hope that some of this information will serve as good news to pregnant or soon-to-be pregnant individuals with ADHD. While the information contained here should never be a substitute for personal medical advice, I want you to leave with the fact that, at least as of now, the overall risks of birth defects or complications remain relatively low for most ADHD drugs. This is especially true when other non-prescribed chemical substances are avoided.

ADHD medications and Pregnancy

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Tuesday, October 14, 2008

Medication Concerns Surrounding ADHD and Epilepsy

Medication strategies for ADHD Comorbid Disorders

In a previous post, we briefly discussed the challenge of medicating ADHD with a common coexisting disorder, namely Tourette's Syndrome. We saw that conventional medications that are often used in the first line of treatment for ADHD are often counterproductive if they make the accompanying disorders worse. Additionally, certain ADHD medications can pose increase risks or dangers to some of these co-occurring disorders. Several articles have been published on stimulant medications and their overall effectiveness and safety for epileptic patients. In this post, we will examine some of the strategies and concerns associated with treating Epilepsy occurring alongside of ADHD. We will tackle some of these medication questions in the second half of the post. However, in order to do this, however, we must first begin by discussing some relevant information surrounding the range, severity and diversity of the symptoms and underlying causes of these two disorders.

Like Tourette's, the disorder of Epilepsy also finds itself to be overlapping (or "comorbid") with ADHD. According to a study reported in the journal Archives of Disease in Childhood in 2005 done by Tan and Appleton, over 20% of individuals diagnosed with epilepsy have multiple symptoms of ADHD. Epilepsy, which is characterized by the presence of recurring seizures that are not provoked by external chemical or environmental triggers, is potentially the most dangerous comorbid disorder associated with ADHD. Further complicating this combination of disorders is the fact that a number of independent studies have linked stimulant drugs (which are often the primary mode of treatment for ADHD) to lowering threshold levels for seizures. As a precaution, stimulants such as methylphenidate are often avoided whenever possible in seizure-prone individuals.

However, relatively new evidence has shown that this may not necessarily be the case with regards to ADHD and comorbid epilepsy. It is important to note that a large number of studies linking stimulant ADHD medications to increased rates of seizures involved more "anecdotal" evidence of symptoms based on relatively small, non-random samples of individuals. While this information should not discredit the validity of these studies, it is important to realize that these studies do not carry the same amount of scientific "weight" as those of larger, randomized, population-based clinical trials.

Further complicating the issue is the fact that there are multiple subtypes, classifications and severity levels of epilepsy. For example, one of the milder forms of pediatric epilepsy is called CAE. CAE, which is short for Childhood Onset Absence Epilepsy, is characterized by short periods (typically less than 10 seconds) of lapses in consciousness, and is often accompanied by rapid or twitching eye movements. Unlike more severe cases of epilepsy, CAE is followed by an immediate full recovery in the individual. These short lapses, when not noticed or carefully observed are sometimes erroneously misread as ADHD since they do temporarily shut down memory, focus and attention, mimicking common ADHD traits.

Since the two disorders typically involve a completely different set of chemical signals, CAE individuals erroneously medicated for ADHD will naturally see little improvement with regards to either disorder. Of course, most competent trained professionals should easily be able to differentiate between the two (CAE episodes can typically be triggered and observed by inducing hyperventilation in a clinical setting, so a non-CAE individual with ADHD can quickly be separated out by this common procedure). Nevertheless, I feel that this possible misdiagnosis can be overlooked and is still worth mentioning. Also of interest in observing these two disorders is the fact that there is a gender bias for each one, although the biases are skewed in opposite directions. ADHD is seen much more often in boys than in girls (some medical professionals claim this ratio to be as high 4 to 1), while CAE is seen more frequently in girls.

Another common (and typically benign) form of epilepsy is called Centrotemporal or Rolandic Spikes. This form is often associated more with lack of facial control (partial facial paralysis and drooling), and physical speech impairments. It is believed that brain activity in many of these individuals, especially between episodes, is connected to a reduced attention span, similar to that of an ADHD individual.

Muddying this issue even further is the fact that these spikes are frequently seen in individuals who fall within the spectrum of autism. While diagnostic methods prohibit an individual from being concurrently labeled as both "ADHD" and "Autistic" (i.e., diagnostic criteria can only allow an individual to be labeled as one or the other but not both), it is important to note the large overlap of symptoms between the two. In other words, we have seen three disorders that all share a number of common overlapping symptoms.

These three disorders may even share a common genetic background. A genetic region on the 3rd chromosome identified as NHE9, has been suggested as having a possible association with ADHD. Another nearby region on the same chromosome has been tied to both autism and epilepsy, suggesting a strong possibility that all three disorders are at least in part tied down to a common genetic region. Since all three disorders are unique and often involve completely different sets of medications, it is easy to see that a misdiagnosis followed by a "mis-medication" can have profoundly negative consequences. With regards to this post, this means that individuals who do have ADHD and (appropriately) take stimulant medications may still see a relatively high frequency of epileptic symptoms, but these are often due to a common (and potentially genetic) underlying condition, and are often not due to the actual stimulant medications being administered for ADHD.

While there is the possibility of genetic overlap between ADHD and epilepsy, the two disorders typically follow completely different chemical pathways. ADHD is closely tied to two neuro-chemical signaling agents called dopamine and norepinephrine (also called noradrenaline), while epilepsy is typically tied to the neurochemicals Gamma Aminobutyric Acid (GABA), as well as Glutamic Acid and Aspartic Acid (both of which are dietary amino acids, and are chemically similar to the questionable food flavoring MSG). Nevertheless, it is true that stimulant medications that are used to treat ADHD (such as Concerta or Ritalin), have been shown to counteract the effectiveness of some traditional anti-seizure medications, namely phenobarbitone (also referred to as BAN, Luminal or phenobarbital). However, these earlier-version anti-seizure medications are often replaced by newer Anti-Epileptic Drugs (AED's), most of which don't have these negative drug interactions.

Additionally, several studies have actually pointed towards ADHD stimulant medications helping with seizure-potentiating conditions. For example, in a 1992 article in the Journal of Clinical Psychiatry, Wroblewski and coworkers observed that seizure-prone individuals with brain injuries actually saw a reduction in the number of episodes following the administration of the common ADHD stimulant methylphenidate. However, other related studies have failed to support these results.

Finally, it is also important to at least mention the possibility that stimulant medications used to treat ADHD may trigger seizures due to their well-known effects on the sleep cycle. While the exact causes of epileptic seizures are still unknown, it is worth mentioning that around half of these episodes occur either during or around periods of sleep. Additionally, sleep deprivation has been shown to increase the likelihood of seizures. It is my personal belief that we should never downplay these important facts and observations.

What I have really hoped to accomplish in this post is to provide you with a bit more background info surrounding ADHD stimulant medications and how some of the data connecting these drugs to increased seizures and epileptic episodes were acquired. Nevertheless, this was not meant to refute all claims that there is an increase risk of epilepsy that is involved by taking these medications, especially for those prone to seizures. Caution and careful monitoring by your physician are still paramount. It is my hope, and my main objective to simply arm you with a bit more information about these drugs, how they work, and how these common ADHD prescription medications can interfere with comorbid disorders such as epilepsy. Look for future posts for more "special cases" involving ADHD and other accompanying disorders.

ADHD medications

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Monday, October 6, 2008

Medication with Atomoxetine for ADHD and Tourette's

ADHD medication

ADHD and Tourette's? Try Strattera (Atomoxetine)

One of the most difficult things about ADD and ADHD is that these disorders are often accompanied by other disorders (called comorbids). One of these disorders is Tourette's Syndrome. Tourette's is actually has a spectrum in and of itself, and can include behaviors such as twitches, tics, vocal "spurts", erratic movements, and in some cases, impulsive foul language. What makes Tourette's so interesting is that it tends to bridge the gap between disorders that are often found on opposite sides of the spectrum with regards to brain chemistry.

Over half of Tourette's individuals are also co-diagnosed with either ADD/ADHD or OCD (obsessive compulsive disorder). For individuals seeking treatment, the number of individuals with Tourette's that also have ADD or ADHD may be as high as 80%, according to some studies. ADHD is typically associated with low levels of the brain chemical dopamine in the front part of the brain, and high levels of serotonin. The latter, OCD, is typically affiliated with low serotonin and higher dopamine levels. Tourette's fits somewhere in between these two, from both a chemical and symptom-based standpoint.

Although there are a number of treatment options out there for ADHD, finding one that is effective in also treating the comorbid symptoms and disorders is also crucial. One of the reasons is that stimulants (such as Ritalin, Dexedrine, Adderall, or Concerta) often make several of the Tourette's symptoms, such as motor or vocal tics, worse. However, non-stimulant ADHD medications show some potential for treating these comorbid disorders. A likely reason is a different underlying chemical mechanism than that of stimulants. Several studies have indicated that the non-stimulant ADHD medication Strattera (Atomoxetine) has also been an effective treatment for Tourette's.

Although other drugs, such as Clonidine, have been tried and displayed positive results for a number of studies. However, Clonidine has also shown side effects such as sedation (drowsiness) in several different cases. While stimulants still serve as the primary mode of treatment for ADHD, we must be careful when the disorder is accompanied by other comorbid disorders, such as Tourette's. If this is the case, then non-stimulant medications such as Atomoxetine must be considered as viable alternatives in the ADHD medication world.

ADHD medications

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