Using Zinc to Boost Ritalin's Effectiveness

We have seen that combining stimulant and non-stimulant medications for ADHD can be effective, as evidenced in a previous post on how Risperidone boosts ADHD stimulant medication effectiveness. We have also explored how supplementation with the amino acid tyrosine can boost the effectiveness of clozapine. Now we will be examining another non-medication compound, zinc sulfate and its effects on the popular ADHD drug methylphenidate (Ritalin, Concerta).

Most of the information in this post is gleaned from a 2004 article in the journal BMC Psychiatry on Zinc Sulfate and methylphenidate for children with ADHD. Some key points are listed below:

• The study compared children with ADHD of both genders, ages 5-11 who took either: methylphenidate with zinc sulfate (15 mg zinc) to those who took methylphenidate by itself (with a sugar placebo) for 6 weeks. Results on treatment effectiveness were determined based on both parent and teacher ratings for ADHD behaviors, as well as psychiatrist evaluations every 2 weeks.


• Zinc is required for the proper function of over 100 different enzymes in the body and previous research has shown that a deficiency in this important mineral can be associated with ADHD.


• Zinc also helps regulate levels of the important compound melatonin, which plays a significant role in regulating sleep patterns in individuals both with or without ADHD. Melatonin also plays an important role in regulating levels of the brain chemical dopamine, which is a key factor in ADHD.


• All children in the sample were of the combined subtype (one of the 3 major subtypes of ADHD, which includes hyperactivity, impulsive behavior and inattention), and had not received previous ADHD medications.

• The study found that ADHD symptoms decreased following the 6 week period for the methylphenidate group, but an even more pronounced decrease in negative symptoms when the methylphenidate was combined with zinc. These trends were statistically significant in both the parent and teacher rating studies.

• (Blogger's point, not from article): Based on previous studies and blog posts on the ADHD stimulant medication Adderall, we have seen that psychiatrists generally see even greater levels of improvements for ADHD treatments than do parents or teachers. If this trend holds true to this treatment, then it is possible that these positive effects may be under-representations of the real potential of zinc-methylphenidate combination treatment.

• (Blogger's remark, not from article): While this study showed promise, it did not compare zinc-methylphenidate treatment to zinc treatment by itself. In other words, we cannot tell if zinc treatment actually amplifies the effects of the medication or if it simply targets additional symptoms of the disorder. Given the fact that zinc deficiency is common in individuals with ADHD, it may be the case that zinc supplementation, not methylphenidate may be the main effective treatment factor. Look for future posts on zinc supplementation and ADHD.

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.

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!