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.

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.

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!

Are ADHD Stimulant Drugs Bad for your Heart?

Potential Cardiovascular Risks of ADHD Medications

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.

ADHD Medication Recall: Dextroamphetamine Sulfate

ADHD Medications

ETHEX Corp. voluntarily recalls batches of Dextroamphetamine Sulfate

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