Monday, November 10, 2008

Increasing Concerta Medication Dosage: Benefits and Risks

In the last post, we introduced the concept of dosage windows for ADHD medications. In other words, we see that the dosage level of an ADHD medication can be of equal importance to the type of medication used. For more info on this topic, please check out the blog site of Dr. Charles Parker called CorePsychBlog. It is extremely well-organized, concise, and easy to follow, in my humble opinion. This is where I was first introduced to the "window" concept of medications, the term which I have borrowed for the last couple of posts.

This post is meant to expound on the dosage principle in the context of on of the more popular ADHD stimulant medications currently on the market, Concerta (slow-release methylphenidate). We will be drawing information from a few key articles, including one from the 2003 Journal of Pediatrics by Mark A. Stein and coworkers. A copy of the original online journal containing a summary of this article can be found here.

If you do not have time to read all of this post, feel free to skip to the last paragraph at the bottom of the page to get the overall message of this blog entry. If you are looking for more detail, I have addressed the key points made in this article in the major points below:

  • The drug Concerta releases the active methylphenidate ingredient into the system at slowly increasing levels over roughly a 12-hour period. The overall effect is similar to that of the traditional tri-daily methylphenidate medication.

  • The article studied the positive and negative effects of this medication in 5 to 16 year-old children under three different common prescription doses, 18, 36 and 54 milligram doses. These children were of average or above-average IQ, with about 1/3 being diagnosed as Learning Disabled. About two-thirds of the children had never taken any type of stimulant medication for ADHD before the study.

  • Noticeable differences were seen between different ADHD subtypes. For the Inattentive subtype, lower levels doses were optimal, while for the Combined subtype (inattention plus impulsive behavior plus hyperactivity), higher amounts were typically optimal. When the effects of co-occuring disorders such as oppositional defiance (ODD) and learning disabilities were factored out to focus in the ADHD itself, the subtype differences were even greater. This underscores the need for proper subtype diagnosis as opposed to just labeling an individual ADHD.

  • For the Primarily Inattentive (PI) subtype of ADHD, the inattention difficulties improved most dramatically with the first 18 mg of medication. Beyond this dosage, only slight effects were seen. This is in agreement with another earlier study which analyzed different doses of another form of methylphenidate for treating ADHD. For the accompanying hyperactivity and impulsive behavioral symptoms (which are often present in the inattentive subtype, just not at the same elevated level of the Combined subtype) were most effectively reduced with the first 18 mg of the medication. While the effectiveness of higher doses leveled off, slight but noticeable improvements were also seen as medication dosage was increased from 18 to 36 mg. At 54 mg, however, improvements stopped or even regressed. This suggests that the "sweet spot" for the Inattentive Subtype of ADHD is somewhere around 18 mg (or slightly higher). Note that Concerta is also available in the 27 mg level, a dosage which was not tested in the study.

  • In contrast to the Inattentive Subtype, where the greatest gains were seen from 0 to 18 mg of Concerta, for the Combined Subtype of ADHD, the greatest overall boost in effectivness was seen between 36 to 54 mg. Based on the trends of the graphs in the paper, as well as data from other studies, it appears that doses beyond 54 mg may still be of benefit for several individuals with the combined subtype. In other words, treatment of individuals with the Combined ADHD Subtype typically requires at least 18 mg more medication than those of the Inattentive Subtype (see note at end of the post for an important caveat and exception to this).

  • Negative side effects of the medication were minimal at low (18 mg) to middle (36 mg) doses. However, beyond 36 mg, these negative side effects became more pronounced.

  • Sleep problems (such as insomnia) began at the 36 mg dosage for Concerta, with the most pronounced effects seen in younger and smaller children.

  • Noticeable appetite suppression was seen even at low doses (from 0 to 18 mg), especially for younger and smaller children. However, the overall severity of this was limited. However, the percentage of children who experienced "severe" appetite suppression dramatically increased between 36 to 54 mg treatments of Concerta.

  • At 36 mg, the presence of or increase in tics (see related post on ADHD and tics) was seen, and a further increase was seen for some children at the 54 mg dosage.

  • A much earlier study on the ADHD medication methylphenidate (an earlier non-Concerta form) suggested that while hyperactive behavior continued to improve at higher doses, the ability to perform cognitive tasks decreased at higher levels of medication. While these effects were difficult to duplicate in future studies, it does suggest an upper limit for certain medications in which going above may lead to a reduction in improvement. We have seen similar effects in previous posts (see the "upside down U curve" in point #6 for tyrosine and clozapine treatment for ADHD here as an example).

A caveat and final blogger's note: Based on the conclusions of the study, it appears that going above the 54 mg limit may be beneficial for certain individuals of the Combined Subtype. While the data of the study may support this, it is important to note that the study only lasted 3 weeks. As a result, long-term effects of high doses of medication were unable to be observed. Additionally, we saw in one of the points above that negative side effects began to creep in at the 36-54 mg level. Based on other blog posts with regards to risk factors of certain ADHD medications as well as potential medication side effects, I urge you to err on the side of caution, especially on issues concerning young and small children (who are at much greater risk for developing severe side effects). In the above study, the highest dosage (54 mg of Concerta) was omitted for the smallest study participant as a precautionary measure.

A quick overall summary of this post: It is imperative that we take ADHD subtype seriously. The take-home message of this blog post should be that lower doses of methylphenidate are often optimal individuals with the Inattentive subtype for ADHD, while those of the Hyperactive-Impulsive (not studied in the above journal article) and Combined subtypes of ADHD typically require significantly higher levels of medication.

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I don't think it's ADHD, but every night I found myself have a difficulty to fall asleep, even if I have sleep apnea. So, I should feel very tired in the evening, which is true.
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