ADHD: Parent information sheet

The term attention-deficit hyperactivity disorder (ADHD) was introduced in 1987 in the new edition of the Diagnostic and Statistical Manual-III-R, published by the American Psychiatric Association. The change in terminology calls attention to the essential features of the syndrome: developmentally inappropriate inattention, impulsivity, and hyperactivity (when present). The confusion surrounding this entity is reflected in the variety of terms used in the past: hyperkinetic reaction of childhood, hyperkinetic syndrome, hyperactive child syndrome, minimal brain damage, minimal brain dysfunction (MBD), minimal cerebral dysfunction, minor cerebral dysfunction, and functional behavior problem (FBP), among others.

Associated or secondary features vary according to age and include obstinacy, stubbornness, negativism, bossiness, bullying, mood swings, excitability with a tendency to overreact, low frustration tolerance, temper outbursts, low self-esteem, and lack of response to discipline. Also encountered are coordination problems, speech impairment, perceptual disorders, and learning difficulties. ADHD is found in 3% of prepubertal children in the U.S., and is approximately 10 times more common in boys than in girls.

The onset of ADHD is typically by age 3, although frequently the disorder does not come to professional attention until the child enters school. Academic difficulties are common and social functioning is often impaired. Family patterns are disrupted by the child, and there is a fairly strong likelihood that one of the parents has, or had, ADHD (suggesting a genetic or hereditary pattern). In some cases the disorder is self-limited and disappears around puberty. In others it continues into adolescence and throughout adult life. With many, the hyperactivity disappears at a certain point, but the attention problems and impulsivity persist.

DRUGS USED FOR ADHD

I. Stimulant Drugs

A. Amphetamines

• Amphetamine
• Dextroamphetamine
• Methamphetamine
• Benzedrine®
• Dexedrine®
• Desoxyn®, Methedrine®

B. Non-Amphetamines

• Methylphenidate
• Pemoline Ritalin®
• Cylert®

II. Antidepressant Drugs

• Imipramine
• Tofranil®

DRUG TREATMENT
The history of stimulant drug use dates back to the discovery by Bradley in 1937 of the therapeutic effects of Benzedrine® on behaviorally disturbed children. In 1948, Dexedrine® was introduced, with the advantage of having equal efficacy at half the dose. Ritalin® was released in 1954 with the hope that it would have fewer side effects and less abuse potential. Although they were initially also popular as antidepressants and diet pills, stimulant drugs are rarely used for those purposes today.

In 1957, Laufer described the "hyperkinetic im-pulse disorder," which he believed was caused by a maturational lag in the development of the central nervous system. He asserted that stimulant drugs were the treatment of choice for this disorder, and postulated that they acted by stimulating the mid-brain, placing it in a more synchronous balance with the outer cerebral cortex. This was an oversimplification, but the exact mechanism of action of these drugs is still unknown.

The most frequently used of the stimulant drugs is Ritalin®, followed by Dexedrine®, Desoxyn®, Ben-zedrine®, and Cylert®. Dexedrine®, Benzedrine®, and Desoxyn® are amphetamine preparations; Ritalin® and Cylert® are nonamphetamines. Cylert® works differently from the other drugs, taking 2-4 weeks before therapeutic effects are noted. Tofranil® is an antidepressant that is also used to treat bedwetting, panic disorders, school phobia, and ADHD. Various dietary programs have been attempted, including the Feingold program (curtailing food additives), low sugar diets, vegetarian diets, etc. None of these dietary regimens have proven to be successful when put to careful scientific scrutiny.

MODE OF DRUG ACTION
It is postulated that stimulant drugs act by affecting the catecholamine neurotransmitters (especially dopamine) in the brain. Some believe that ADHD develops from a dopamine deficiency, which can be corrected by stimulant drug treatment. At one time it was felt that the stimulant drugs created a paradoxical (opposite and unexpected) reaction (calming and sedation) in ADHD youngsters, and that this response was diagnostic. This is no longer believed to be the case, as the response to stimulant drugs is neither paradoxical, nor specific. Children with conduct disorders and no evidence of ADHD may also respond to these drugs. Likewise, studies with normal and enuretic (bedwetting) children have shown that many experience a calming effect rather than the expected stimulation.

Because of their relative safety, the stimulant drugs remain the treatment of choice in treating ADHD. The drugs are unquestionably successful in decreasing hyperactivity, lessening impulsivity, and improving attention span in approximately 70% of those treated. As a result of improved interactions with family members, peers, and teachers, the drug-treated children feel better about themselves, and self-esteem rises. At the present time, however, there is some controversy as to the degree of learning and memory improvement resulting from the treatment of ADHD children with stimulant drugs. Overall, the ideal approach is one in which the children are involved in individual, group, or family therapy, along with drug treatment.

CONTRAINDICATIONS

1. Known hypersensitivity or allergic reaction to the drug.
2. Seizure history.
3. Glaucoma.
4. Hypertension.
5. History of tics.
6. Hyperthyroidism.
7. Pregnancy.

DRUG INTERACTIONS
The drugs may decrease the effects of some antihypertensive drugs (e.g., Ismelin®). They should be used cautiously with pressor agents (adrenalin-like drugs). They may affect the liver metabolism of certain anticoagulants, anticonvulsants, and tricyclic antidepressants. Insulin requirements in diabetic patients may be altered when the drugs are co-mixed.

PRESCRIBING INFORMATION
Ritalin® is available in 5, 10, and 20 mg tablets. A new preparation, Ritalin® SR®, is a sustained-release product with effects lasting 6-8 hours (twice as long as the standard preparation). The usual starting dosage of the standard Ritalin® for children under 8 is a single 5 mg tablet in the morning, and for children over 8 is a single 10 mg tablet in the morning. Each week the daily dosage can be increased by 5 mg and 10 mg a day, respectively. Usually the tablets are taken at breakfast and lunch; occasionally an after-school dose is necessary. The tablets should be taken on an empty stomach, ½ hour before or after meals. The total maximum dosage should not exceed 60 mg, although under extreme situations 80 mg/day dosages are prescribed.

There has been little experience with the sustained-release SR® preparation. One study showed that it was as effective as the shorter-acting preparation, and had no difference in side effects. The SR® preparation comes in 20 mg tablets, roughly equal to two of the standard 10 mg tablets taken 4 hours apart. Generally, the initial dosage adjustments are done with the standard preparation, which is later switched to the SR® brand for maintenance treatment.

The amphetamines are quite similar in their pharmacological makeup. Dexedrine® comes in 5, 10, and 15 mg tablets and capsules; in a liquid elixir preparation with 5 mg per teaspoon; and in slow-release capsules of 5, 10, and 15 mg. The dosage is approximately half that of Ritalin®. Benzedrine is available in 5, 10, and 15 mg tablets; and in a 15 mg sustained-release capsule. The dosage range is similar to Dexedrine® (S-60 mg/day). Desoxyn® is available in 2.5 and S mg tablets; and in 5, 10, and 15 mg sustained-release capsules. Pharmacological actions are similar to those of Dexedrine® and Benzedrine®.

Cylert® is given once a day, giving it an advantage over the shorter-acting preparations. It has a gradual onset of action; significant clinical benefits may not be evident until the 3rd or 4th week of treatment and they may take as long as 6 weeks. The drug is available in 18.75, 37.5, and 75 mg tablets; and in 37.5 mg chewable tablets. The recommended starting dose is 37.5 mg, and the dosage is increased in daily increments of 18.75 mg per week until the desired clinical effects are reached. The effective daily dose for most patients is in the range between 56.25-75 mg. The maximum daily dose is 112.5 mg.

Of those ADHD-children treated with stimulant drugs, 66%-75% will improve and 5%-10% will get worse. It is always important to verify that the medication is actually being taken, as some children will refuse to do so as a means of rebellion or defiance. There is a marked variation in drug response among different children, and even within an individual child on different days. Some children will not respond unless they are placed on extremely high doses, or on 4-5 doses a day, probably as a result of accelerated metabolism (drug breakdown).

Tolerance to the stimulant drugs may develop, requiring an increase in dosage after the child has maintained nicely on a particular dosage for a year or so. Children who respond to one of these stimulant drugs will probably respond as well to any of the others. There are cases, however, in which a child will respond favorably to one drug but not another. Also, there is no evidence that children treated for years with stimulant drugs will have a greater likelihood of abusing drugs or narcotics during their adolescent years.

SIDE EFFECTS
The most common side effects encountered with stimulant drugs are: loss of appetite, weight loss, sleeping problems, irritability, restlessness, stomachache, headache, rapid heart rate, elevated blood pressure, sudden deterioration of behavior, and symptoms of depression with sadness, crying, and withdrawn behavior. Two of the most disconcerting side effects are the intensification of tics (muscle twitches of the face and other parts of the body), and suppression of growth. It is rare that stimulant drugs cause tics, but they may activate an underlying (latent) tic condition. There is some concern that this could even lead to a severe tic condition called Tour-ette's Syndrome. As a result, ADHD children with tics are often treated with the neuroleptic tranquilizer, Haldol®, either alone or in combination with one of the stimulant drugs (Benzedrine® may be the safest under these circumstances).

The growth retardation problem has caused considerable controversy and concern since an article written in 1972 described suppression in growth of ADHD children who had undergone long-term stimulant drug treatment. Subsequent studies have varied markedly in their findings. One study of adolescents who took the drugs as children showed no growth suppression. Another study demonstrated growth suppression during the 1st year, but none during the 2nd year of drug treatment. Others have demonstrated a rebound growth spurt when the drug is withdrawn, or even in those still taking the medication. There is also some indication that taller children are more vulnerable to growth suppression effects than are those who are smaller. The problems appear to be dose-related, occurring in Dexedrine® doses of 15 mg or more per day, and Ritalin® doses greater than 30-40 mg per day. Experts now believe that any risk of growth suppression in most children is minimal and is mainly in body weight rather than height. Even the effects on weight are small, averaging approximately 2 pounds during the first year.

As a result of the growth retardation scare, many clinicians are suggesting that the drugs be given only on school days and not on weekends, holidays, or vacations. Realistically, most parents are unable to tolerate the deterioration in behavior that ensues when the medication is withdrawn. At the very least, the drugs should be withdrawn once a year to reestablish the need to continue the medication. A popular approach is to discontinue the stimulant drugs during the first 2 weeks of November. If the medication is still required, it will be apparent soon enough, and not too late to endanger the child's grades and reputation among schoolmates and teachers.

Other rare side effects include: irregular heartbeat, hair loss, decreased white blood cell count, anemia, and rash. Elevated liver function tests may be associated with Cylert®. A rare hypersensitivity reaction consists of hives, fever, and easy bruising. Occasionally, ADHD children on stimulant drugs will experience a personality change characterized by dejection, lifelessness, tearfulness, and over sensitivity Conversely, some may develop a state of excitement, confusion, and withdrawal.

 Adapted from The Handbook of Modern Psychopharmacology. Copyright 1983 by BMH Clinical Laboratories.

Reprinted with permission