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Why Are There So Many Different Medications to Treat ADHD?

By: Larry B. Silver, M.D.

ADHD is a neurologically-based disorder resulting from a deficiency of a specific neurotransmitter or group of neurotransmitters in specific areas of the brain. Neurotransmitters are the chemicals in the spaces between nerve cells (i.e., the synapses) that transmit signals from one nerve cell to the next.

The primary neurotransmitter involved is called norepinephrine. Two of the building blocks needed to produce this neurotransmitter, dopa and dopamine, are also involved. The purpose of the primary medications used to treat ADHD is to stimulate specific cells within the brain to produce more of the deficient neurotransmitter. Because of this role, these medications are called, "stimulants."

The primary medications used to treat ADHD stimulate these nerve cells to produce more of the deficient neurotransmitter. There is a small group of other medications, the "non-stimulants," that use a different mechanism to raise the level of the deficient neurotransmitter. These medications appear to slow down how quickly the transmitter is broken down and re-absorbed, resulting in it staying in the synapse longer and thus increasing the amount present. (They will be discussed later.)

There are two primary stimulant medications: methylphenidate and dextroamphetamine. (These are the "generic" forms of the products.) Each has been used since the 1960s or earlier. All other medications are variations on these two medications. Each variation has a trade name. These stimulants might be designed using different release mechanisms, absorption sites, or doses. Pharmaceutical companies use different trade names for their ADHD medications; thus, there are many products advertised to treat ADHD. Each, however, is basically one of these generic products.

The purpose of this article is to clarify the confusion many parents and medication users have about the many different medication products on the market because of the competitive advertisements parents are exposed to. I will first discuss the stimulant medications and then the non-stimulant medications.

The stimulant medications

As noted above, all current stimulant medications derive from either methylphenidate or from dextroamphetamine. There are several points of information needed before I discuss the specific medications. It is these points that often lead to confusion by parents and by users.

For each medication, there are several important characteristics. First is the target dose expected to be in the blood, and thus the brain, at any one time. The second is the release mechanism and, thus, the length of time the medication will remain available and active.

If a pharmaceutical company can establish a different chemical formulation or mix or a different release mechanism, it can seek Food and Drug Administration (FDA) approval for the medication to treat ADHD. If approved, each product can be given a specific brand name, even if the medication is not new, but only has a new release mechanism.

The target dose: Each product releases a specific amount of the medication into the blood over a given period of time. The FDA requires that the number value for each product represent the total amount of the medication in the tablet/liquid/capsule/patch and not the amount in the blood.

Thus, if, for example, methylphenidate is in the form of a four-hour tablet and releases 5 mg over that time, it is called methylphenidate 5 mg. If the medication is in the form of an eight-hour capsule, let's say, Adderal XR, about half of the dose is released immediately and about half of the dose is released about four hours later. A capsule that releases 10 mg immediately and 10 mg four hours later would be called Adderal XR20. Do not be confused by the number assigned to the prescription. This number represents the total amount of the medication in the product and not the amount in the blood stream at any one time. (The number for the dose of the twelve-hour capsule is confusing and will be described below.)

The release mechanism: Each of these medications might come in the form of a tablet that releases all of the medication within about an hour. That medication will last about four hours. They also may come in a form that lasts about eight hours. This form could be an eight-hour tablet that releases about half of its contents immediately and half about four hours later. Or it might be an eight-hour capsule with tiny pellets inside. These pellets are designed to release about half of the product immediately and half about four hours later.

One product is designed to last 12 hours. The capsule does not dissolve. Within the capsule there is a sponge on the bottom, the medication on top, and a tiny hole above the medication. As the capsule passes through the gastrointestinal track and absorbs moisture, the sponge expands and slowly pushes the medication out of the hole. The number value assigned to each dose is confusing. If the goal is to release 5 mg consistently over 12 hours, then there must be 15 mg in the capsule. However, it takes time for the sponge to become moist enough to start to expand. Thus, an initial release of medication is needed to last until the sponge is in operation. Research determine that 3 mg would work. Thus, to release 5 mg over 12 hours, one needs the initial 3 mg plus 5 mg every four hours for the 12 hours. The total is 18; thus, the medication is called Concerta 18 (5 + 5 + 5 + 3). It does not release 18 mg at a time but 5 mg. To release 10 mg over this time requires the 10 mg per four hours plus a starter dose of 6 mg; thus, it is called Concerta 36 (10 + 10 + 10 + 6). The capsule that releases 15 mg per four hours requires a starter dose of 9 mg; thus, it is called Concerta 54 (15 + 15 + 15 + 9).

Some products are liquid. The information provided will state how much medication is in each unit of liquid; for example, 5 mg per 5 ml of liquid. One product is released by a dermal patch through the skin into the bloodstream. It should start to work in about one hour and last until about one hour after being removed (usually after nine hours). The number assigned represents the total amount in the patch and not the amount released during any period of time.

One final clarification on the different products available relates to the structural image of the medication when seen under a polarized light. This light causes the chemical to produce two images: the right image (called the dextro- form) and the left image (called the levo-form). Thus, must medications can be made as a dextro- and a levo- product. For example, the basic amphetamine products used initially for this disorder were studied. It was learned that the dextro form was potent and the levo form was not. Thus, "dextro-amphetamine" became the primary product used. Recently, a similar study was done on methylphenidate. It was found that the dextro form was potent and the levo form was not. Thus, dextro-methylphenidate was manufactured under the name of Focalin. Same core product but more potent. Another example relates to the product, Adderall. It was produced by mixing "several salts of amphetamine" - the dextro-form (known to be potent), the levo form (believed not to be potent), and "other amphetamine salts."

Now, we are ready to discuss the "Stimulant" medications.

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The methylphenidate family of medications

Current formulations of methylphenidate are:

  • Methylphenidate (generic form)
  • Ritalin (brand name)
  • Metadate (specific brand form)
  • Methylin (brand liquid form)
  • Concerta (brand 12-hour release)
  • Focalin (brand dextro-methylphenidate)
  • Datrana (brand methylphenidate patch)

Methylphenidate is available in the form of a liquid, four-hour tablet, eight-hour tablet, eight-hour capsule, 12-hour capsule, and an eight-hour dermal patch. Thus:

  • liquid (Methylin)
  • a four-hour tablet as 5 mg, 10 mg, or 20 mg
  • an eight-hour tablet as Ritalin SR or Metadate ER
  • an eight-hour capsule as Ritalin LA or Metadate CD
  • a twelve-hour capsule as Concerta
  • an eight-hour Dermal Patch as Datrana 10, 15, 20, 30

Focalin (dextro-methylphenidate) is available as:

  • a four-hour tablet
  • an eight-hour capsule, called Focalin XR

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The Dextro-amphetamine family of medications

Dextro-amphetamine is now available in the generic form and in the newer mixture of amphetamine salts, Adderall.

Dextro-amphetamine is available as:

  • a four-hour tablet
  • an eight-hour capsule (spansule)
  • an oral solution, (brand Procentra)

Adderall is available as:

  • a four-hour tablet
  • an eight-hour capsule (called Adderall XR)
  • a slower-to-be-absorbed capsule called Vyvance in 20 mg, 30mg, 40 mg, 50 mg, 60 mg and 70 mg strengths

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The non-stimulant medications

The Beta Blockers: One group of non-stimulant medications is called "beta blockers." They are most often used to lower blood pressure. These medications appear to raise the level of norepinephrine by slowing down how quickly this transmitter is broken down and absorbed within the synapse. They are seen as an adjunct to the stimulants; that is, as increasing their effectiveness. Most studies suggest that these medications work best on the impulsive behaviors, thus the disruptive behaviors. The established medications are: clonidine and guanafacin.

Clonidine, also know by it's trade name, Catapress is often sedating. Thus, it may be difficult to use during the day. Many clinicians might use it at bedtime, taking advantage of its sedating effect in an effort to counteract the problem falling asleep often found with the stimulant medications. It comes in 0.1, 0.2, and 0.3 mg tablets.

Guanafacin, also know by its trade name, Tenex, is used to treat tic disorders. Some studies suggest that it might help to address the impulsivity and behavioral difficulties found with ADHD. It comes in a 1 mg and a 2 mg tablet. At the time this article was prepared, a new brand product of guanafacin was introduced. The unique feature is that it comes in an eight-hour extended-release tablet. Because the release mechanism is different, it can be marketed as a new product, called Intuniv. The manufacturer notes that it is to be used to treat ADHD. At this time, there are little data on the studies done or the intended action. The literature provided states that the efficacy is based on two eight- to nine-week studies. It is not known how effective the drug is after nine weeks. It is suggested that Intuniv might best help address the disruptive behavioral problems found with some individuals with ADHD. No studies have been done yet on children. Thus, I will defer any comments on the use of Intuniv with children who have ADHD.

Atomoxetine: This medication is available as Strattera. It appears to work by slowing the breakdown and absorption of norepinephrine in the synapse. It also may impact on the level of a different neurotransmitter, serotonin. Strattera is given once a day and is meant to last the full day. Strattera is available in 10, 18, 25, 40, and 60 mg tablets. The proper dose for each individual must be determined by increasing the dose until benefits are noted. Clinical feedback suggests that the results of Strattera in addressing the behaviors of ADHD have not been consistently positive.

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Summary

There are many medications available to treat ADHD. Most of the effective medications are in the "stimulant" group. However, there are non-stimulant medications to be considered.

These many medications are products of a few chemical compounds that, over the past forty years, have been shown to successfully treat ADHD: methylphenidate and amphetamine. There are many medications used to treat ADHD because each of these basic two generic medications is available in many variations. Each may have a different chemical structure, mix of products, or release mechanism. And, each may have a different brand name, often in different doses and with different release mechanism.

It is hoped that this article will help parents and users of medication to treat ADHD to understand why there appear to be so many different medications available. The reality is that there are only a few medications that treat ADHD, but many variations on the theme.

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This article was written by Dr. Larry Silver exclusively for LDOnLine.