Stimulant Medication and AD/HD
Carol Watkins, M.D.
What are the Stimulants? When we talk about the use of stimulant medications in psychiatry, we generally are referring to methylphenidate (Ritalin) amphetamine (Dexedrine, Adderall) methamphetamine (Desoxyn) and pemoline (Cylert.) The first two are by far the most commonly prescribed. The stimulant medications increase the release or block the reabsorption of dopamine and norepinephrine, two brain neurotransmitters. This increases the transmission between certain neurons. Each stimulant has these effects in slightly different ways. Thus each may have similar or different effects on the AD/HD symptoms of a given individual. A recent study (using specially bred mice) reported in the Jan. 1999 issue of Science (1) suggests that methylphenidate elevates levels of serotonin, and that this may account for some of its calming effects.
There have been many studies showing the effectiveness of stimulants in children, adolescents and adults. Generally, stimulants effectively decrease inattention, distractibility, over activity and impulsivity in three quarters of individuals with AD/HD.
AD/HD and the Brain: Self-regulation and attention are complex phenomena. There are different types of attention, including selective attention, sustained attention, strategy development, flexibility and response inhibition. Researchers are just at the beginning of their attempts to understand how different types of attention correlate with brain anatomy and physiology. However, research has shown some differences between the brain functioning of individuals with AD/HD and that of normal subjects. Individuals with brain injury to the frontal lobes of the brain may show attention problems similar to those of AD/HD adults.
A study done at NIMH showed that boys with AD/HD had a smaller prefrontal cortex, (part of the brain just behind the eyes and forehead) caudate nucleus and globus pallidus. The latter two structures are located deeper in the brain. Xavier Castellanos, M.D. compared the prefrontal cortex to the brain’s steering wheel with the caudate nucleus and the globus pallidus as the accelerator and the brakes. (2) These size differences are just averages. One cannot use a brain scan to diagnose AD/HD.
Other differences in brain activity and function have been found. It is believed that the transmission of dopamine and norepinephrine in the circuits between the frontal cortex and deeper brain structures play an important role in AD/HD.
Stimulants are best known for their use in treating AD/HD. However, they have been used in several other conditions.
Rapid Acting Stimulants: Methylphenidate is the most commonly prescribed stimulant. It is approved for use in individuals ages six and older. It usually starts to work about 15 to 30 minutes after it is taken. It peaks an average of 90-120 minutes after it is taken. This can vary from one individual to another. The effect of a dose can be from 2.5 to 4 hours. Amphetamine (Dexedrine) is approved for ages 3 and older. It is also short acting but usually lasts an hour or so longer than methylphenidate.
It is important to remember the short duration of these medications. Many individuals take a morning dose of methylphenidate at 6:30 and a second dose at Noon. This person may have little medication effect in the late morning. A school might assume that a child is misbehaving for a particular teacher when it is actually a temporary lack of medication.
Longer Duration Stimulants:
Methylphenidate (Ritalin) is a short-acting drug. It can be difficult to remember several doses per day. Ritalin SR often seems to show inconsistent results. It only comes in 20mg pills and cannot be split into smaller fragments. Metadate-ER, manufactured by Celltech, was released in 10mg and 20mg sizes. Metadate-ER is similar to Ritalin-SR. The active component, methylphenidate, is in a wax-like matrix that releases the drug over time. Celltech more recently released Metadate CD which uses a different delivery system. Its peak effect is generally around 5 hours and its effect lasts 8 hours. Metadate CD encapsulates the methylphenidate in two types of beads. About 30% of the medication is released immediately. The remainder is released over time through beads with a release-control membrane. Concerta (Alza Pharmaceuticals) is a form of Methylphenidate that uses an osmotic system to deliver methylphenidate in a pulsed pattern. This allows a 12 hour response from a single daily dose. Concerta was released in August 2000. The osmotic “oros” system has been used successfully for several years for a diabetes medication and a bladder control medication. With Concerta, the methylphenidate level does not rise as fast as it would with Metadate CD, but the Concerta lasts longer than Metadate CD or Ritalin SR. Drug studies suggest that its duration of action is 12 hours, but I have seen a number of patients who seem to get a shorter duration of effect at all dosage levels. Novartis, the manufacturer of brand name Ritalin, has released a non-racemic form of methylphenidate, called Focalin. Other forms of methylphenidate such as Concerta and Metadate are mixtures of two mirror images (isomers) of the methylphenidate molecule. The body may metabolize the dextro (right handed) form of a compound differently from its mirror image the levo (left handed) form. In the case of methylphenidate, the dextro isomer is more active than the levo isomer. Thus, Novartis recommends that when you switch from regular methylphenidate to Focalin, you start with half as much Focalin.
Dexedrine Spansules, a long-acting form of d-amphetamine, has been on the market for years. It has a peak effect in 1-4 hours and lasts 6-10 hours. It tends to have a more gradual tapering and thus may have less of a rebound effect. Adderall is a mixture of four salts of d-amphetamine combined with a smaller amount of the less active r-amphetamine. Some clinicians felt that Adderall had a longer duration of action than regular d-amphetamine. However, there are as of yet, no published studies showing that it lasts any longer than short-acting d-amphetamine. Thus we cannot really classify regular Adderall as a long-acting stimulant. However, in November 2001, Shire, the manufacturer of Adderall, released Adderall XR. In this formulation, the Adderall is encapsulated in coated beads inside of a capsule. Half of the beads dissolve immediately, and the other half dissolve about 4-6 hours later. There are, as yet, no published studies comparing Adderall XR to the less expensive Dexedrine Spansules. However, I have found the Adderall XR useful for patients who cannot swallow pills. Shire has looked at the metabolism of Adderall XR when the capsule is opened and the beads are sprinkled on pudding.
For individuals who have difficulty swallowing pills A significant number of individuals have difficulty swallowing pills. This is more common in children and the elderly, but some adults also have trouble with some of the larger pills. Crushing some forms of stimulants may change rate of absorption or duration of action. However there are now two forms of extended release stimulants that have been studied when sprinkled on food. Adderall XR showed a similar duration of action when the capsule was opened and the contents were sprinkled on pudding. A recent study showed that Metadate CD, when opened and sprinkled on applesauce, showed similar onset and duration of action as the intact capsule.
Stimulant Medications: Duration of Action
Table adapted from Greenhill, Laurence, “Are New Stimulants Really Better?” AACAP Oct. 2001 Annual Meeting
Pemoline (Cylert) is approved for ages 6 and older. It takes about one or two hours to take effect and lasts up to eight hours. Permoline may take days to build up enough to have an effect. It should be given seven days a week. There have been 15 deaths due to liver failure associated with pemoline. It is now a second-line medication for AD/HD. Individuals who take it need to have periodic blood tests.
Methamphetamine (Desoxyn) may be effective in some individuals who do not respond to the other stimulants. It has a higher potential for abuse than the other stimulants. Used carefully in selected patients, it can be an effective treatment for AD/HD.
Are Stimulants Addictive? The Food and Drug Administration (FDA) has classified the stimulants, except for Cylert, as Schedule II. This means that the physician cannot write for automatic medication refills. Schedule II medications generally have a higher potential for abuse than most other types of medication. Some people worry that they might become addicted to stimulants. If individuals take their medication as prescribed, the potential for addiction to methylphenidate or amphetamine is fairly low. Methylphenidate is absorbed into the brain much more slowly than a compound like cocaine. This is why methylphenidate does not produce the high experienced in drugs of abuse. A study published in Pediatrics in 1999, (3) showed that individuals with AD/HD who were treated with stimulant medication had a lower risk of drug abuse than AD/HD individuals who had not taken medication. Still we are cautious about prescribing stimulants to individuals who are abusing drugs. Injecting stimulants intravenously, inhaling them or mixing them with illegal drugs can lead to further substance abuse.
Stimulant Side Effects Many individuals take stimulants with few side effects. Others experience mild problems and some are unable to tolerate stimulants. Often we can treat annoying side effects so the individual can continue to take the stimulant.
Using Stimulants to Treat AD/HD: Stimulants can decrease the inattention, hyperactivity, and impulsivity associated with AD/HD It is important to do a careful history and mental status examination before starting an adult or child on stimulant medication. We often get outside data such as relatives’ reports or school checklists to help verify the diagnosis. Inattention is a fairly non-specific phenomenon. It may be caused by anxiety, depression or medical illness. Some people may have another psychiatric condition on top of their AD/HD. Conversely; AD/HD can be mistaken for depression anxiety or laziness.
Five or Seven Days Per Week? In the past, children often got medication coverage only for the hours they were in school. Some clinicians still use stimulants only for school or work situations. We prefer a more individualized approach. Attention deficit disorder affects individuals differently depending on the type of activity, and the severity and type of the AD/HD. Some people have mild AD/HD or have learned to compensate in most situations. Such an individual might take a short acting stimulant only to cover school or difficult work situations. Even in these situations, three doses of methylphenidate are often better than two larger doses.
Other individuals benefit from broader stimulant coverage. Impulsivity can be problematic in the evenings and on the weekends. Children and adolescents may need to concentrate to do their homework in the evenings or on weekends. Sometimes we need to prescribe a longer acting stimulant twice a day. Those who truly need coverage 24 hours per day may need to use one of the antidepressants.
We often start a patient out with a single dose of methylphenidate. This allows the individual to compare the way he feels on and off the medication. We start with a low dose and gradually increase the number and size of the doses until we reach a satisfactory response or run into side effects. It may be embarrassing or inconvenient for someone to take 3 or 4 doses of medication each day. Even people without AD/HD have trouble remembering to take medication this often! We may move to a longer acting stimulant such as Adderall or Dexedrine Spansules. As time goes on, we “fine tune” the size and frequency of the medication doses. Some people take the same dose every day. Others may take a lower dose on weekends.
Some adults with AD/HD may need to use a pillbox or other reminders to help them remember to take their medication. Children and adolescents should have their medication supervised and dispensed by an adult.
Substance Abusers with AD/HD: Adolescents and adults with AD/HD are at increased risk for substance abuse. Methylphenidate can be abused by crushing it and using it intranasally. When an individual has both AD/HD and a drug problem, treatment becomes more complex. Reducing the person’s impulsivity may make it easier for him to make safe choices. However, we do not want him combining stimulants with alcohol or illegal substances. Thus, we try to avoid using methylphenidate and the other Schedule II medications in individuals who are active substance abusers. Instead, we may try to treat their AD/HD with an antidepressant. If these are not effective, we are left with a dilemma. If the patient makes a commitment to stay clean and if we have a way of monitoring him, we can cautiously prescribe stimulants.
Are Stimulants Over-Prescribed? According to a study by Safer et al (1995) (4) the use of methylphenidate has more than doubled between 1990 and 1995 in the U.S. About 2.8% of children between the ages of 5 and 18 are taking methylphenidate for AD/HD. AD/HD is diagnosed more frequently in the U.S. than in most other countries. Most researchers believe that this is due to an increased awareness of AD/HD, not an actual increase in the number of individuals affected. Does this mean that the stimulants are over-prescribed in America? This has been a matter for hot debate.
Some individuals have an incomplete response to stimulants. Others cannot tolerate the stimulants. See Non-stimulant medication Treatment for AD/HD and New Medications for AD/HD.
Article updated January 2002.
1. Gainetdov et al., Role of Serotonin in the Paradoxical Calming Effect of Psychostimulants on Hyperactivity, Science, Jan. 15, 1999: 397-410.
2. Castellanos, FX, et al, Quantitative Brain Magnetic Imaging in Attention Deficit Hyperactivity Disorder, Archives of General Psychiatry, July 53 (7) 607-616, 1996.
3. Biederman et al, Pharmacotherapy of Attention Deficit/Hyperactivity Disorder Reduces Risk for Substance Abuse Disorder, Pediatrics, Vol 104, No 2, August 1999.
4. Safer, et al, Increased Methylphenidate Usage for Attention Deficit Disorder in the 1990s.Pediatrics, Dec. 1996.
5. Practice Parameters for the Assessment and Treatment of Children, Adolescents and Adults with Attention Deficit/Hyperactivity Disorder Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 36, No 10, S, 1997.
6. Goodman and Gilman’s The Pharmacological Basis of Therapeutics 9th Edition, Goodman, Limbird, Milnoff, Gilman and Hardman, McGraw Hill Publishers, 1996.
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Northern County Psychiatric Associates
Our practice has experience in the treatment of Attention Deficit disorder (ADD or ADHD), Depression, Separation Anxiety Disorder, Obsessive-Compulsive Disorder, and other psychiatric conditions. We are located in Northern Baltimore County and serve the Baltimore County, Carroll County and Harford County areas in Maryland. Since we are near the Pennsylvania border, we also serve the York County area. Our services include psychotherapy, psychiatric evaluations, medication management, and family therapy. We treat children, adults, and the elderly.
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Carol E. Watkins, M.D.
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