Features Index

CHILDREN AND PSYCHOTROPIC DRUGS

BY MARY ANN LITTELL

Few situations are more difficult for families to cope with than a child suffering from a behavioral or emotional disorder – whether it is a toddler with autism, a preteen suffering from attention deficit disorder, or a clinically depressed teenager. Often, the troubled youngster is friendless, unable to learn and develop normally. Social and family problems arise, and the child's world spins even more out of control.

The prevalence of pediatric mental illness is greater than many people realize. According to a new report from Surgeon General David Satcher, MD, one in ten children suffers from mental illnesses severe enough to impair development. But fewer than one in five children get medical treatment for any mental health problems.

There are serious consequences. Kids become alienated from family and peers, flunk out of school, commit crimes, maybe even land in prison, where mental health services simply don't exist. A juvenile detention center cited in the report found over two-thirds of its youthful offenders suffered from psychiatric disorders. "When we don't respond, children are dumped into the juvenile justice system, in special education classes, or on welfare," says Satcher. "Clearly it is a crisis."

"Some 12 to 13 percent of children and adolescents have a diagnosable mental disorder – and in 3 percent of those cases, the disorder is serious," says Robert Hendren, DO, professor of pediatrics and psychiatry at UMDNJ-Robert Wood Johnson Medical School. "The most important question is: How many of these children can be helped?"

Traditionally, mental health treatment for children relied upon behavioral or talk therapy, often coupled with an attitude of "waiting until they grow out of it." However, treatment options have changed dramatically since the 1970s. For today's children suffering from mental or behavioral disorders, psychotropic medications can work miracles.

"Many of the medicines we're using are actually refined versions of earlier products," explains Charles Cartwright, MD, assistant professor of psychiatry at UMDNJ-New Jersey Medical School (NJMS). "Where the previous generation of drugs affected many different receptors in the brain, the new ones target more specific receptors. They are making a considerable difference in helping control disturbing symtoms and behaviors, producing results that in the past were not possible."

Physicians also have greater precision in diagnosing mental illness than they did years ago. "We can identify problems earlier and more quickly," says Hendren. "By treating children at a younger age, we hope to improve their quality of life both now and in the long-term." Early intervention for many behavioral or emotional disorders is thought to fend off post-traumatic stress disorder, attention deficit hyperactivity disorder (ADHD), and depression, which frequently begin in childhood and adolescence.

USING PSYCHOTROPIC DRUGS "OFF-LABEL"

Millions of American youngsters take psychotropic drugs for a variety of mental disorders. There is no question that many children have greatly benefited. However, these drugs were developed for adults, not children. Most have not been tested for pediatric use, and have not been approved by the Food and Drug Administration (FDA) for treatment of children. Some 75 to 80 percent of psychotropic drugs are used "off label"– prescribed for a different use than approved by the FDA.

Clearly, more research is needed to study the effects of psychotropic medications on children. The National Institutes of Health now requires that children be part of all their clinical trials, unless there is a good reason not to include them. The NIH has also established several multi-site trials to facilitate pediatric testing. To encourage further research, the FDA even offers financial incentives: It will extend the patents of drugs by six months if the pharmaceutical company conducts pediatric studies with them.

Many drug companies have responded, stepping up their clinical trials for children – even though the hoped-for positive results don't always pan out. A recent pediatric trial for BuSpar, successfully used to treat generalized anxiety disorder (GAD) in adults, found that it was not particularly helpful in treating certain types of anxiety in children. "What works for adults is often inappropriate for kids," says Hendren. "That's why more testing is needed – preferably in an academic setting, so we can learn about the science of using these drugs on the immature brain."

Hendren, who is also director of child and adolescent psychiatry at UMDNJ's University Behavioral HealthCare (UBHC) is currently directing several children's studies (see chart, page 31).

RITALIN AND ADHD

The most commonly prescribed drugs for children are the psycho-

stimulants, which include Ritalin, Adderall and Dexedrine (see chart above). These medications are used to treat ADHD and other disorders. They have been shown to be effective in large treatment trials with children and adolescents. Some six million prescriptions for Ritalin are filled annually.

While Ritalin has been extensively tested for children, its widespread use has become controversial. A recent flurry of lawsuits charge that ADHD is being overdiagnosed to boost Ritalin sales to children who are merely unruly.

Many health professionals take issue with this criticism. "While concern about the overuse of Ritalin is appropriate, the drug has helped millions of children," states Cartwright. "Sometimes it is hard to discern whether a child is merely rambunctious or has a diagnosable problem, such as ADHD. Before any child is prescribed a psychostimulant such as Ritalin, a comprehensive evaluation involving parents, the child, and his or her teachers must be completed."

In UBHC's Newark-based Child & Adolescent Extended Outpatient Psychiatry Service, some 550 patients ages 6 to 17 are treated for behavioral and emotional disorders. Stephanie Hamarman, MD, assistant professor of psychiatry at NJMS, is medical director of the service. Some patients come to the facility once every one to four weeks; others come even more frequently. At first they are usually treated with non-medication therapies, including individual and family counseling and behavior modification. When those treatments alone are deemed unsuccessful, medications are considered.

Mental disorders can be difficult to assess, particularly when the patient is a child, says Hamarman. "Making the diagnosis can't be done in one short visit," she explains. "It usually requires several in-depth visits with a mental health professional. We also get the input of parents and schools, because they see the child in different environments. For example, behavior at school is highly structured, with more limits and rules. Is the child able to adapt? If not, medication may help."

TARGETING DEPRESSION

Antidepressants are the second largest group of drugs prescribed for children under 18 years of age. An earlier generation, tricyclic antidepressants, included Elavil and Toframil. These drugs had some serious, and occasionally fatal, side effects. The newer ones, including those called SSRIs (selective serotonin reuptake inhibitors), are more easily tolerated, but have not been widely tested on children.

SSRIs include Prozac, Paxil, Zoloft, Celexa and Luvox. They help regulate levels of serotonin, a chemical in the body that is believed to affect mood. Serotonin levels drop off during early adolescence, and therefore may be related to depression in this age group. Low serotonin levels have also been linked to substance abuse problems in teens.

"Before any treatment is started, it's important to make an accurate diagnosis," says Hamarman. "We look at several factors. Is there a family history of depression? Has a child had two or more major episodes of depression, or just occasional times when he or she feels bad?"

Both Hendren and Hamarman cite good results in treating children and adolescents with antidepressants. The drugs are widely prescribed by pediatricians and primary care physicians. In general, Hendren believes that mental disorders are most accurately diagnosed by child and adolescent psychiatrists or other pediatric specialists. However, given the realities of managed care, many children with mental or behavioral problems are not referred to specialists.

In a recent study, 72 percent of family physicians and pediatricians said they had prescribed SSRIs to patients under the age of 18. Yet only 8 percent said they had received adequate training in managing childhood depression, and only 16 percent said they were "comfortable" treating depressed children. Many health professionals believe the more powerful psychotropic drugs are best left in the hands of specialists.

MEDICATING PRESCHOOLERS

While much media attention has focused on mental disorders in adolescents, increasing numbers of very young children are also taking antidepressants and stimulants. According to a recent study of more than 200,000 preschoolers published in JAMA, the number of 2 to 4 year olds taking psychotropic drugs, including Ritalin and Prozac, rose 50 percent between 1991 and 1995.

"Deciding when to medicate a very young child is a tough call," says Hendren. "We don't want to give kids pills to 'fix' them or take away aspects of their personality that we find distracting." He rarely prescribes psychotropic medication to children under the age of 6, with one notable exception: the case of a 4 year old child with bipolar disorder whose behavior was disturbed and violent. The child's parents, who also had bipolar disorder, brought him to UBHC and requested medication to help control his symptoms. He showed some improvement on Depakote, a medication that stabilizes mood. Throughout treatment, he was carefully monitored by his parents and physicians.

At UBHC, very young patients taking psychotropic medications often spend time in therapeutic nurseries in both Newark and Piscataway, where they are watched by health care professionals.

Such caution is necessary with young patients. Current theories of neurodevelopment look at brain growth as "plastic." It can be changed or modified, depending on various factors in the environment, including medication. UMDNJ researchers are particularly interested in the effects of psychotropic drugs on children's developing brains. "Coupling drug trials with neuroimaging studies enables us to study physical changes in the brain that may be caused by medication," says Hendren.

To illustrate his point, he cites recent MRI studies of children with OCD (obsessive-compulsive disorder). In children who were untreated, the caudate, a part of the basal ganglia in the brain, was shown to be enlarged. After treatment with Paxil, the caudate had shrunk to normal size.

Robert Hendren, DO, professor of pediatrics and psychiatry at RWJMS, is currently directing several children's studies with psychotropic drugs.

The same research group then studied a different group of children with the same disorder, treating them with behavior modification rather than the drug. The end result was the same as the group treated with Paxil – shrinkage of the caudate. "Medications may give you a more rapid result, and sometimes that's what you want –particularly when a child has very serious symptoms," says Hendren. "But medication is not the only way to get a result."

MORE "MIRACLE" DRUGS

Haldol and Thorazine (made famous, or infamous, in the movie "One Flew Over the Cuckoo's Nest") were once touted as wonder drugs. However, they have such strong side effects that they are felt to be too "heavy-duty" for children. The newer atypical neuroleptics are easier to

tolerate and show real promise in treating children with psychotic and other emotional disorders. They include Risperdal and Zyprexa (for bipolar disorder). "Side effects include weight gain and fatigue, and they are sometimes significant," says Cartwright.

In the past 10 years, great progress has also been made in treating OCD with medications. Some of the most effective are Luvox, Anafranil and Zoloft. Typically, the drugs, which are FDA-approved for children, are used in combination with cognitive-behavior therapy and family therapy.

Children with OCD display many obsessions often involving worries about dirt, germs or bad things happening, and compulsions, such as touching objects repetitively, checking and arranging things. "It is very rewarding to treat OCD, because you see such definitive results," says Cartwright. "With the right combination of medication and behavior therapy, the symptoms can be reduced by 30 to 40 percent."

In addition, in many cases the benefits of treatment can be long-lasting and medication dosages can be reduced without a deterioration in the OCD symptoms. Longitudinal studies are needed to evaluate the safety and long-term effectiveness of these medications in children.

Cartwright, who is also director of the Program for Research and Treatment of Autism and Related Disorders in the department of psychiatry at NJMS, says many psychotropic drugs, including Risperdal, Paxil, Prozac and Zyprexa, are being used to control some of the symptoms of autism. "While there is no FDA-approved medication for the treatment of autism, a large number of children with autism are helped by taking medication to control problems like aggression, hyperactivity, and compulsive behavior," he says.

Hendren is testing another drug, Tomoxetine, on children ages 6 to 18 with ADHD. There are 19 children in the study, and early results are good, he believes. The drug, which has some of the characteristics of antidepressants, is not yet on the market. It is also being tested on adults with ADHD, with equally promising indications.

Mood stabilizers, including Depakote, Tegretol and Neurontin, are also being used to help impulse control, mood instability and anxiety. "The drugs are effective in calming kids down, and so far, have been found to be relatively safe," says Hendren. "But they are not medications to be prescribed casually."

A major benefit of psychotropic medications is that they help children be more amenable to other therapies. "For kids who are severely impaired, the right medication can level the playing field," says Hamarman. "The children are more receptive to learning and behavior modification. They do better in school and at home."

Do some kids in fact "grow out" of mental illness? That all depends on the child, the disorder, and the treatment. About half of children with ADHD will continue with the disorder as adults. Depression also recurs in many adults who reported at least one serious episode in childhood. However, Hendren believes that today's more refined medications have more long-lasting positive results than did their predecessors. He sees a brighter future for children and adolescents with mental and behavioral disorders. "More longitudinal studies are needed to evaluate the benefits of medications over a long period of time," he says. "But it's gratifying to see some of my patients entering middle adolescence medication-free."

For information on clinical trials mentioned in this article, contact Pat Kirshenblatt at 732-235-4059.

COMMONLY PRESCRIBED PSYCHOTROPICS

CATEGORY

DRUGS

SYMPTOMS

SSRIs (selective serotonin reuptake inhibitors)

Fluoxetine (Prozac); Paroxetine (Paxil); Sertraline (Zoloft); Fluvoxamine (Luvox); Citalopram (Celexa)

Anxiety, depression, impulsivity, obsession, compulsion, anger, separation anxiety

Stimulants

Methylphenidate (Ritalin, Methylin); Dextroamphetamine (Dexedrine, Adderall); Pemoline (Cylert); Tomoxetine

Those of ADHD: inattention, distractibility, behavior problems

Adrenergic stimulating agents

Clonidine (Catapres); Tenex

Anxiety, sleep disturbance, hyperactivity, impulsivity

Atypical neuroleptics

Risperidone (Risperdal); Olanzapine (Zyprexa); Quetiapine (Seroquel); Clozapine (Clozaril)

Social awkwardness, withdrawal, tics, obsession, compulsion, behavior problems

Mood stabilizers

Valproic acid (Depakote, Depakane); Carbamazepine (Tegretol); lithium carbonate (Lithobid, Lithostat); Gabapentin (Neurontin)

Mood instability, temper tantrums, anger, depression, behavior problems

Others

Buspirone (BuSpar); Bupropion (Wellbutrin); Propranolol (Inderal)

Anxiety, depression, ADHD, impulsive aggression


ONGOING PEDIATRIC STUDIES AT UBHC/RWJMS

DRUG

DISORDER

MANUFACTURER

Olanzapine (Zyprexa)

children and adolescents with bipolar disorder

Lilly Research Laboratories, Inc.

Olanzapine (Zyprexa)

children with severe emotional disturbance

Lilly Research Laboratories, Inc.

Citalopram (Celexa)

children and adolescents with depression

Forest Laboratories

Tomoxetine Hydrochloride

children ages 6 to 18 with depression

Lilly Research Laboratories, Inc.

Sertraline (Zoloft)

children and adolescents with major depressive disorder

Pfizer, Inc.

Paroxetine (Paxil)

multicenter, placebo-controlled study of children and adolescents with obsessive compulsive disorder

SmithKline Beecham Pharmaceuticals, Inc.

Venlafaxine (Effexor) children with generalized anxiety disorder (GAD) Wyeth-Ayerst Laboratories
Venlafaxine (Effexor) children with social phobia Wyeth-Ayerst Laboratories
Risperidone (Risperdal) children with psychosis Janssen Pharmaceutica

PRINCIPAL INVESTIGATOR: ROBERT HENDREN, DO

 


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