154th Annual Meeting of the American Psychiatric Association,May 8, 2001
Does Your Child Have Obsessive-Compulsive Disorder?
November 29, 2002 02:59:21 AM PST, KidsHealth.org
"What if I forget to bring my homework to school? Did I remember to feed my goldfish? I know I turned off the TV, but let me check to make sure."
All children have worries and doubts. But when your child can't stop thinking about them, they begin to hamper his ability to function. No matter how stressful the worries are, no matter how silly they may seem, and no matter how much your child wants them to go away, they do not subside on their own. In association with this anxiety, your child may begin to perform certain rituals, behaviors that are performed in a certain way over and over again. If these behaviors persist, your child may be diagnosed with obsessive-compulsive disorder (OCD).
It is reported that approximately 1 million children and adolescents in the United States suffer from OCD. This translates to one in 200 children. OCD is more prevalent than many other childhood disorders or illnesses, but it is often hidden because it causes pain and embarrassment to the child.
In the years when most children want to fit in with their peers, the discomfort and stress brought on by OCD can make them feel scared, out of control, and alone.
What can you do to help? Keep reading to learn more about OCD and how you can help your child.
What Is OCD?
OCD is an anxiety disorder in which the brain gets stuck on a particular thought or urge and can't let go. OCD manifests itself in obsessive thinking or beliefs that tell a child: "If you don't do X, then something uncomfortable or even life-threatening will happen." (In younger children, compulsive behaviors may be evident without the "if...then" thinking.) The rise in anxiety or worry is so strong that the child must perform the task or dwell on the thought, over and over again, to the point where it interferes with everyday life. OCD can become extremely embarrassing and overwhelming for both the child and his family.
Experts aren't sure how OCD gets started, but it should never be viewed as the child's fault or something he can stop if he just tries harder. OCD is a disorder, just like a sleep disorder or dyslexia - it's not something the child can control. Experts do know that OCD tends to run in families, and just like in children, OCD in adults is often kept private so that most families are not aware of this disorder in their family histories.
OCD is best viewed as a "short circuit" in the brain's "worry computer," says John March, MD, author of OCD in Children and Adolescents: A Cognitive Behavioral Treatment Manual. This worry computer inappropriately and repeatedly cues the child to fear that something will happen. These cues are commonly called obsessions.
Obsessions are repeated thoughts or impulses that are out of place - they cause the child to experience anxiety or distress. They are out of the child's control, and they are different from normal thoughts. A child with these thoughts usually attempts to ignore or suppress obsessive thoughts or impulses by neutralizing them with another thought or action - a compulsion. For example, a child who is plagued with doubts about having turned off the stove might compulsively check the stove, again and again, to ensure that it is off.
Compulsions, or rituals, are the deliberate and repeated behaviors a child with OCD performs to relieve the anxiety caused by the obsessive thoughts. For example, a child who has a fear of germs may repeatedly wash his hands until the skin becomes raw; a child who has an obsession with neatness will redo her test paper so many times that she may tear a hole in it from constant erasing. Other times, compulsions might seem less clearly related to the obsessive thought.
Common OCD Behaviors in Children
OCD can make daily life difficult for children and families. The behaviors often take up a great deal of time and energy, making it more difficult to complete tasks such as homework or chores or enjoy life. In addition to feeling frustrated or guilty for not being able to control their own thoughts or actions, children with OCD also may suffer from low self-esteem because the disorder can lead to shame or embarrassment. Children often involve their parents in their rituals (for example, asking about a potential illness they think they have), leading to increases in family stress.
Children with OCD may feel pressured because they don't have enough time to do everything. They might become irritable because they have to stay awake late into the night or miss an activity or outing to complete their rituals. They might have difficulties with attention or concentration because of the intrusive thoughts.
In addition, obsessions and compulsions related to food are common. These can lead to abnormal eating habits (such as eating only one kind of food), thus compromising nutrition.
Studies of children and adolescents with OCD have revealed that the most common obsessions include:
fear of dirt or germs
fear of contamination
a need for symmetry, order, and precision
preoccupation with body wastes
lucky and unlucky numbers
sexual or aggressive thoughts
fear of illness or harm coming to oneself or relatives
preoccupation with household items
intrusive sounds or words
How Does Breakfast Affect Stimulant Treatment for ADHD?
Brown University Child and Adolescent Psychopharmacology Update 4(10):1, 6-7, 2002. © 2002 Manisses Communications Group, Inc.
Researchers recently compared the pharmacokinetic effects of food on two long-acting stimulants used in the treatment of attention-deficit/hyperactivity disorder (ADHD): osmotic-controlled release methylphenidate (Concerta) and extended-release mixed amphetamine salts (Adderall XR). They found that while drug exposure for this formulation of methylphenidate is not affected by eating a high-fat breakfast, drug exposure in the first hours after dosing with the extended-release formulation of amphetamine salts was markedly reduced when subjects ate such a breakfast. The researchers suggest that variation in early drug exposure may be clinically important, especially where drug administration is meant to cover the first eight hours of the school- or work-day.
The study was conducted by Cathy K. Gelotte, Ph.D., Executive Director of Medical and Regulatory Product Development at McNeil Consumer & Specialty Pharmaceuticals (marketers of Concerta), and colleagues. The randomized, single-dose, open-label trial was conducted with a four-treatment, crossover design. Healthy adults (ages 18 to 50 years old) received either methylphenidate 36 mg or amphetamine salts 20 mg in the morning after either an overnight fast or a high-fat breakfast. (The high-fat breakfast consisted of two eggs fried in butter, two slices of toast with butter, two strips of bacon, 4 ounces of hash brown potatoes and 8 ounces of whole milk.)
The researchers compared drug exposure at hours 4, 6, and 8 by measuring partial areas under the concentration-time curve (AUC0-4, AUC0-6, AUC0-8). Total exposure (area under the curve calculated to infinity, AUCINF), maximum concentration (CMAX) and time to maximum concentration (TMAX) were also calculated. In accordance with Food and Drug Administration (FDA) guidance, there was considered to be no "food effect" if drug exposure remained within ±20 percent whether the subject fasted or ate.
The drug labeling for Adderall XR notes that, while food does not affect the extent of absorption, it does prolong the time to maximum concentration by 2.5 hours after eating a high-fat meal (from 5.2 to 7.7 hours). Existing trials with Concerta, on the other hand, have found no difference in pharmacokinetics or pharmacodynamics when taken after a high-fat breakfast.
"We wanted to look at extended-release formulations because there are so many of them on the market," said Gelotte. "We had an idea that early exposure might be an issue because of the shift in TMAX noted in the drug labeling [for Adderall XR]."
Thirty-six subjects completed all four treatments (of the 39 that were enrolled, two were withdrawn for positive drug screens and one due to problems with blood collections).
The researchers found that while the differences between fed and fasted exposure to methylphenidate fell within the 20 percent range, there were marked reductions in early drug exposure to amphetamine salts when the subjects had eaten breakfast.
For measures of overall extent of exposure (AUCINF and CMAX), the researchers findings did not contradict early findings of similar exposure in fasted or fed conditions.
According to Gelotte, the differences found in the CAFE study are due to differences between the respective drug-delivery systems.
The OROS system utilized by Concerta consists of an "osmotic pump." After the first 22 percent of the drug dissolves for the tablet's overcoat, water enters the semi-permeable inner shell and forces the remainder of the methylphenidate dose out of a hole in one end of the tablet.
According to Gelotte, the OROS system means that methylphenidate is continuously released as a liquid from the stomach into the intestines, where it is absorbed into the blood. The two kinds of extended-release beads which make up Adderall XR (50% immediate release and 50% delayed release) are large enough that they are held back in the stomach with food and only released into the intestines periodically, Gelotte said.
Asked about the clinical significance of these findings, Gelotte said, "I think that's a hard question to answer. The study was designed to examine differences in delivery of the drug and blood levels." The relationship between exposure to a drug and therapeutic benefit from the drug is not one-to-one, and it may vary by individual patient as well as by drug or drug delivery system. "I think the key is that they [clinical efficacy and drug level] are not directly correlated."
However, the difference might be meaningful if individual patients, who are titrated to a specific efficacious dose, experience fluctuations in drug exposure.
"When you have a food effect this marked -- and we were surprised how marked it was -- it's like giving half the drug," noted Gelotte.
Steven Pliszka, M.D., Associate Professor and Chief of the Division of Child and Adolescent Psychiatry at the University of Texas Health Science Center, San Antonio, says more research needs to be done to clarify these findings.
"I think people should take note of this data. I think there should be a follow up of this study in kids or adults with ADHD looking at clinical outcomes," Pliszka said.
"It has not been my experience -- with all types of stimulants -- that there has been an effect of eating," Pliszka continued. Referring to the lower level of early exposure to amphetamine found in the CAFE study, Pliszka says, "We have to ask what is ADHD symptoms. What appears to be small levels may be clinically adequate."
Pliszka prescribes both methylphenidate and amphetamine salts for ADHD in clinical practice. No studies have shown that certain patients respond better to one stimulant or the other. "There are no clinical predictors of response or non-response at this point," said Pliszka.
Likewise, no studies have shown differential patterns in side effects and prescribers mostly rely on individual experience when choosing a stimulant medication, said Pliszka.
In the CAFE study, the researchers noted that no subject withdrew from the study due to an adverse event (AE). The most frequently reported AEs for methylphenidate were headache, nausea, and decreased appetite, while the most frequently reported for amphetamine were headache, insomnia, light-headedness, pruritus and decrease appetite. In total, 55 mild AEs were reported by 22 subjects (13 of those by one subject). For methylphenidate, 22 AEs were reported and 21 were considered to be to be possibly-to-likely related to treatment. For amphetamine, 33 AEs were reported and 22 were considered to be possibly-to-likely related to treatment.
Neither Gelotte nor Pliszka are aware of any studies currently being conducted to examine clinical outcomes associated with the "food effect" nor of any studies comparing different extended-release formulations of methylphenidate to each other.
Auiler JF, Lynch JM, Gelotte CK: Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) study. Current Medical Research and Opinions 2002; 18:311-316.
Comparison in early exposure between Concerta and Adderall XR
A= Adderall XR; C=Concerta
ADHD: It's Not Just for Kids Anymore
56 minutes ago
By Holly VanScoy
SATURDAY, Oct. 26 (HealthScoutNews) -- As college students settle into the routine of lectures, tests and papers this fall, a surprising number will learn something shocking: They have attention-deficit/hyperactivity disorder.
Once considered primarily a childhood condition, ADHD, as it is commonly called, is now known to be a lifelong condition for as many as half of those troubled with its hallmark symptoms of inattention, distractibility, impulsivity and emotional instability starting before age 7.
Despite its persistence in as much as 1 percent of the population, the disorder often remains undiagnosed for a decade or more, finally becoming debilitating when academic, social or work pressures mount after high school graduation.
That's why ADHD seems to break out like an epidemic on college campuses every fall.
"The structure of high school is such that students with ADHD can slip through unnoticed," says Robert J. Resnick, a professor of psychology at Randolph-Macon College in Ashland, Va. He's also the author of "The Hidden Disorder: The Clinician's Guide to Attention-Deficit/Hyperactivity Disorder in Adults."
"But college is a different story," Resnick adds. "The stepped-up demands of higher education, coupled with the absence of many familiar external structures and controls, bring these students problems with organization and distractibility to the forefront. They just can't fake academic performance any longer. When referred to the college's support services for help, they find out -- many of them for the first time -- that they have had ADHD for many years."
Female college students are just as likely as male students to be affected, despite the disproportionate number of boys diagnosed with ADHD in the early grades, says Resnick, a former president of the American Psychological Association.
"The condition is no respecter of gender," Resnick explains. "However, the symptoms in young males and females are often different. Boys with ADHD tend to be more active and aggressive, which results in earlier referral for assessment by parents and teachers. In elementary school, the ratio of boys diagnosed with ADHD to girls diagnosed is three- or four-to-one. On the college campus, the ratio is one-to-one."
Beth Howlett, clinical coordinator of the Counseling Center at Widner University in Chester, Pa., is familiar with the phenomenon. She estimates that only about one-third of the ADHD students she works with were diagnosed before they began college.
"Elementary and secondary teachers today are doing a better job spotting the symptoms of this disorder early," Howlett says. "But there are still many students, particularly girls, who slip between the cracks before they start college.?
According to Howlett, students with ADHD tend to have a familiar litany of complaints. These include:
Inability to concentrate in class or on homework assignments.
Inability to grasp the meaning of what they've read without repeated re-readings.
Difficulty following a professor's train of thought, paying attention through long lectures or labs, or taking notes in an organized way.
Susceptibility to distractions that don't seem to affect their classmates.
Reliance on stimulants, such as coffee, as a means of focusing on important tasks.
Abusing substances, such as alcohol, illegal drugs or prescription medications, as a means of managing stress.
"What I call the 'burden of reading' -- the sheer volume of mastery of the written word required in virtually every university course -- is one of the first things that shows up as a problem for the college student with untreated ADHD," Howlett says.
Although the official criteria for diagnosing ADHD later in life is identical to those confirming the disorder in young children, it is increasingly recognized that the condition is often more subtly expressed in adulthood.
As a recent article in American Family Physician notes, the "hyperactivity common in ADHD children is less likely to be overt in adults, and the on-the-go drivenness of the ADHD child is frequently described by ADHD adults as restlessness, difficulty relaxing or feeling ?chronically on edge.?"
"ADHD results in clinically significant impairment," Resnick says. "These are not students that experience difficulty paying attention from time to time in class, or occasionally can't remember something important. These are students who are chronically impulsive, distracted and disorganized. They don't forget where they left their car keys. They forget where they left their cars."
According to both Resnick and Howlett, the good news is that ADHD in adults is treatable, using the same behavioral and psychological approaches and medications that help younger patients with ADHD. Medications include methylphenidate (Ritalin (news - web sites)), dextroamphetamine (Dexedrine), pemoline (Cylert), and methamphetamine (Desoxyn).
Under the Americans with Disabilities Act, ADHD college students qualify for a range of accommodations on campus, too, such as therapy, along with assistance organizing their life, study skills, test-taking and securing adequate lecture or laboratory notes from their classes.
Howlett also says ADHD college students appropriately identified and served often fare better academically and socially than their non-ADHD peers.
"When they are diagnosed early and plugged in to the right resources, students with ADHD do well," she says. "But if the ADHD is left untreated, such students often grow increasingly disorganized, impulsive, frustrated and, ultimately, unsuccessful in this very competitive environment."
What To Do
Useful information for college students with ADHD can be found at the Student Alliance on ADHD. For practical tips on the management of ADHD in adults, click here.
Adults with Attention Disorder Show Memory Flaws
Fri Oct 25, 5:25 PM ET
By Paula Moyer
SAN FRANCISCO (Reuters Health) - Adults with attention-deficit/hyperactivity disorder (ADHD) show a different pattern of brain activation when performing memory tasks than adults without the condition, a Massachusetts researcher reported here at the American Academy of Child and Adolescent Psychiatry's annual meeting.
Functional magnetic resonance imaging (fMRI) scans showed that a certain region of the brain normally activated during working memory tasks was not active in ADHD adults. This finding lends further validity to the concern that ADHD symptoms can persist into adulthood, said Dr. Larry Seidman, a staff psychologist and researcher at Massachusetts Mental Health Center and Massachusetts General Hospital in Boston.
"We know that there are brain abnormalities, such as reduced brain volume, in children with ADHD," he told Reuters Health. "We need to know if those abnormalities persist into adulthood." He noted that 30% to 60% of children with ADHD still have symptoms as adults.
The study, which is ongoing, focused on working-memory deficits, which are considered hallmarks of ADHD. The investigators sought to determine whether adults with ADHD differ from controls in activating two parts of the brain, the prefrontal cortex and the anterior cingulate, on a working-memory task.
The initial sample consisted of six people with ADHD and five "controls" without the disorder. The ADHD study participants were all right-handed, native English speakers with IQs of at least 80. They had either normal vision or correction to normal, had been diagnosed with ADHD in childhood, and had a family history of ADHD. Seidman said that he and his team of investigators anticipate that the study sample will grow to include 12 people in each group.
The working memory tests consisted of several tasks that required the individuals to temporarily retain a piece of information in a distracting environment. Two tasks involved counting and articulating colors while coping with distracting information, such as the word "red" printed in blue. Other components of the task required study participants to retrieve information from previous tasks.
Even though the study participants with ADHD were able to complete the tasks, their reaction times were somewhat longer than those of controls, Seidman said. The fMRI studies showed that the anterior cingulate of the brain, which is involved in working memory, failed to activate in ADHD patients, in contrast to controls.
"These findings are consistent with previous research showing excess activation in posterior areas of the brain for ADHD adults and not controls," Seidman said. He noted that the effects of drug treatment for ADHD on brain function are not known.
Researchers Closer to Finding Genetic Cause Of ADHD
By Jennifer Thomas HealthScoutNews Reporter
WEDNESDAY, Oct. 23 (HealthScoutNews) -- Researchers have taken a major step toward finding the genetic underpinnings for attention deficit hyperactivity disorder (ADHD), a discovery they hope will lead to better diagnosis and treatment.
Interestingly, the chromosomal region implicated in ADHD is the same region that previous research has linked to autism, says study author Susan Smalley, co-director of the Center for Neurobehavioral Genetics at the University of California, Los Angeles.
This suggests the two disorders, though they have different symptoms, could share some of the same underlying genetic risk factors, Smalley says.
"It's an intriguing possibility that there could be a common gene that contributes to both," she says. "I won't be surprised if it's the same gene contributing to both, but I certainly don't know for sure."
The study appears in the October issue of the American Journal of Human Genetics.
Smalley and her colleagues spent five years gathering clinical and genetic data on 203 families who had more than one child with ADHD. Using statistical analysis, the researchers identified a series of molecular markers on a region of chromosome 16 among the siblings with ADHD.
The region on chromosome 16 contains about 150 of the 35,000 genes in the human genome (news - web sites). Pinpointing the exact ADHD gene or genes will take additional research, Smalley says.
"All we've done is narrowed down the search from 35,000 genes," she says. "There are still up to 150 genes it could be. Even to find that one, we still have a lot of work to do."
ADHD is the most commonly diagnosed behavioral disorder in children. Though symptoms vary from child to child, it's often characterized by inattention, hyperactivity, impulsiveness, a failure to follow through or plan ahead, and in some cases difficulty maintaining social relationships.
Autism, while a distinct disorder, has some of the same symptoms. Children with autism have problems relating to others. They also have a tendency to perform repetitive movements and develop an obsessive interest in a single subject.
"Either they hardly talk at all or they talk 'at you,' rather than talking 'with you,'" says Dr. Sarah Spence, medical director of the Autism Genetic Resource Exchange, a gene bank for autism research. "No two kids with autism have exactly the same symptoms."
There are some tantalizing similarities between ADHD and autism, says Spence, who was not involved in the just-published research.
Many parents of autistic children report hyperactivity and inattentiveness in their children, emotional outbursts or tantrums, and impulsive behavior. Ritalin (news - web sites) or other stimulants, which are commonly prescribed to treat ADHD, are often used to help autistic children, Spence says.
However, both researchers caution against jumping to conclusions about the genetic similarities.
"It could be that the autism gene is in that group of 150 genes, but it's a completely different gene than the ADHD gene," Spence says.
Not only that, complex disorders such as ADHD and autism are almost surely due to multiple genetic and environmental factors, not a single gene, Smalley says.
Based on their analysis, Smalley and her colleagues estimate the gene or genes on chromosome 16 might account for as much as 30 percent of the genetic cause of ADHD. It's estimated that ADHD is 70 percent to 80 percent genetic, she says.
The hope is that when the exact gene or genes are identified, researchers can then study what role they play in brain functioning and what goes awry in children with ADHD or autism.
From there, they could diagnose the disorders sooner -- and develop better, more effective, treatments, Spence says.
"Once we understand the biology of it better, we can learn to treat it better," she says. "Right now, we're at a bit of a loss for what to do and how to know early on if somebody is going to have ADHD."
New treatments don't just mean medications, Smalley says. Some research has shown environmental factors, including low birth rate and smoking during pregnancy, might put children at risk for ADHD.
Anything from dietary adjustments to finding methods of teaching children with ADHD that are better suited to them could help, she says.
Health - Reuters
Attention Disorder Tied to Impulsive Pill Taking
BOSTON (Reuters Health) - Children with attention-deficit disorder (ADD) are much more likely than kids without the attention problem to be hospitalized for ingesting prescription drugs, according to a new study presented Monday during the American Academy of Pediatrics National Conference.
"We found that ADD is a significant risk factor for pharmaceutical ingestion in children aged 5 to 9," study presenter Dr. Selena Hariharan, clinical fellow of pediatric emergency medicine at Cincinnati Children's Hospital in Cleveland, Ohio, told Reuters Health. "This has not been shown before."
More attention has been focused on toddlers, who may get their hands on a bottle of prescription drugs and take them out of curiosity, and adolescents, who may be interested in prescription drugs for recreational purposes. Hariharan and colleagues found that children with ADD aged 5 to 9 are also at risk for taking prescription drugs inappropriately.
Hariharan and colleagues reviewed the charts of children admitted to their hospital for ingesting prescription drugs during a 4-year period. The team identified 31 such cases, 55% of them in girls, and matched each patient to three "control" patients admitted during the same time period for abdominal pain, appendicitis or gastroenteritis.
Hariharan's team found that 35.5% of the children who were admitted for ingesting prescription drugs had ADD, compared with 6.5% of control patients, who were admitted for other reasons.
Most often, children with ADD who were admitted to the hospital for taking prescription drugs took their own medications (29%) or their parents' medications (29%).
"There has been extensive research into how ADD relates to injury and trauma, but pharmaceutical ingestion has never been specifically looked at," Hariharan told Reuters Health.
She believes that both availability and impulsivity play a role. "Children with ADD have the medications available in the home and they are impulsive," Hariharan said. She said she hopes to "use these studies as a springboard into future research endeavors so that we can then influence the guidance of parents of children newly diagnosed with ADD."
Mon Oct 14, 7:07 PM ET
Different parts of your brain control various aspects of attention, says a study in the October issue of Neuropsychology.
Canadian and American researchers tested the reaction times of 36 people with lesions in their frontal lobes and other parts of their brains. The lesions were caused by trauma, hemorrhage, surgery for benign tumors, and other acute disorders.
The reaction times of the people with the brain lesions were compared to reaction times of 12 healthy people in a control group.
The tests included measuring speed, sensitivity and response differences between study participants as they did tasks such as pressing a button in response to a specific signal. They also gauged how the people in the study sped up or slowed down in response to increasing distraction and redundant information.
When they analyzed the results, the researchers found that different types of attention problems were associated with injuries in different parts of the brain. In particular, they determined that the ability to screen out irrelevant information seems to be based in the frontal lobes' right side.
The results show that attention involves at least three distinct processes that appear to be functionally and anatomically different, the study says. The findings add to scientific evidence that attention is a complex, multi-faceted process.
The findings could help lead to better treatment for people with attention disorders.
How Safe Is Methylphenidate in Preschoolers?
The Brown University Psychopharmacology Update 13(9):2-3, 2002. © 2002 Manisses Communications Group, Inc.
Presently, the U.S. Food and Drug Administration (FDA) has approved the use of methylphenidate only in children at least six years old. However, many prescribers are using the drug off-label in this population. The 2000 publication of a study documenting dramatic increases in prescriptions for psychotropic medications -- especially methylphenidate (Ritalin and others) -- for preschool-age children attracted a lot of attention -- and not just from child psychiatrists. Even then-First Lady Hillary Clinton raised concern over possible over-prescribing of methylphenidate. "Some of these young people have problems that are symptoms of nothing more than childhood or adolescence," she said. Her call for investigation of the safety of methylphenidate helped pave the way for the Preschool ADHD Treatment Study, the first large-scale study of methylphenidate use in young children.
The original study, by Julie Magno Zito, Ph.D., of the School of Pharmacy at the University of Maryland, and colleagues, analyzed ambulatory care prescription records from two state Medicaid programs and a health maintenance organization (HMO) for the years 1991, 1993 and 1995. The researchers examined prescription trends for stimulants, antidepressants and neuroleptics among children ages two to four years.
Zito and colleagues found that among children between two and four years old, the prevalence per 1,000 enrollees was 12.3 for stimulants, 3.2 for antidepressants, 2.3 for clonidine and 0.9 for neuroleptics. Methylphenidate had a prevalence of 11.1, accounting for 90 percent of stimulant use. Moreover, Zito and colleagues found a substantial increase in psychotropic use among preschoolers during this time period, with a 28.2-fold increase in clonidine use, 3-fold increase in stimulant use and 2.2-fold increase in antidepressant use. Neuroleptic use did not increase substantially during this period.
Zito and colleagues noted in their report that "...randomized, double-blind, controlled clinical trials are needed for off-label indications to evaluate dosages, efficacy, and safety of single and multiple agents shown to be commonly used or widely recommended." They concluded, "Unresolved questions involve the long-term safety of psychotropic medications, particularly in light of earlier age of initiation and longer duration of treatment. While it is reassuring that anecdotal reports have rarely documented these problems, the possibility of adverse effects on the developing brain cannot be ruled out."
Reason for Concern
Francisco Xavier Castellanos, M.D., Professor of Child and Adolescent Psychiatry and Director of the Institute of Pediatric Neuroscience at New York University, points to two particular concerns with psychotropic drug use, especially methylphenidate, in young children.
"First we have almost no systematically obtained data. It's happening -- Zito documented that -- but it's happening blind. And it's happening out of necessity, not in a nefarious way.
"The absence of information should make everyone nervous -- and it does," Castellanos continued.
The second major concern Castellanos mentioned is the lack of understanding of the timing of brain development. "Our fundamental lack of knowledge comes into play here. We don't know whether there is a danger point below which we should not be prescribing."
Castellanos notes that two studies published since Zito's study suggest that age does make a difference. The first, by Moll and colleagues, found a reduction in the density of striatal dopamine transporters in adult rats that had been given methylphenidate for two weeks when very young, compared to those given methylphenidate post-puberty. A second study, by Andersen and colleagues, found that rats treated with methylphenidate when young were more sensitive to the aversive effects of cocaine than were those who were administered methylphenidate as adults.
"These two articles make the argument that age of treatment is a factor. It may be a positive effect or a negative effect, but without data, we don't know. These two papers are all that I know, and it's in the animal literature," Castellanos said.
Castellanos also noted that MRI studies comparing medicated and unmedicated children are currently in press, but concluded that our knowledge in this area is still inadequate.
The Preschool ADHD Treatment Study (PATS) is an attempt to address the need for controlled studies of off-label drug use in preschool-age children. The ongoing Phase III study is exploring the safety and efficacy of methylphenidate for ADHD in preschool-age children. Laurence Greenhill, M.D., of the Department of Psychiatry at the New York Psychiatric Institute and Columbia University, is leading a team of researchers in a National Institute of Mental Health (NIMH)-funded study of methylphenidate in this population.
At a presentation at the 2002 American Psychiatric Association meeting, Greenhill noted that there are particular concerns in prescribing to very young children that are qualitatively different from those pertaining to older children. For example, he noted that infants' bodies and metabolism are very different from those of older children, in that they clear drugs much faster and have a greater liver mass relative to their body size.
The PATS study is being conducted at six sites (Columbia University, Johns Hopkins University, Duke University, New York University, the University of California at Irvine and the University of California at Los Angeles), and will enroll 165 children between the ages of three and five-and-one-half. All of the children will participate in 10 weeks of family training in behavioral therapy, and only those who are determined to be insufficiently improved will go on to drug treatment.
During the randomized, double-blind, active-medication phase of the trial, children will be prescribed methylphenidate 1.25, 2.5, 5 or 7.5 mg, administered t.i.d. in capsules made specially for the study. After the appropriate dose has been determined, the children will be monitored for 40 weeks. Data will be collected from both teachers and parents, and most children will be followed for 16 months in order to observe the long-term effects of methylphenidate.
The PATS study has raised a number of ethical issues to the foreground of child psychiatric research. Questions that are raised for all child research are all the more significant in research in young children: Should young children be subjected to clinical trials of drugs, and how can young children consent to participation in such trials given limits to their understanding and ability to communicate their willingness to continue?
The PATS study was scrutinized by the NIMH before the study was funded. In attempting to address these concerns, parents are required to consent at each of the five stages of the study. Additionally, children will be presented with age-appropriate explanations and asked for their consent to continue the trial, too.
The research team anticipates finishing the trial in August 2003.
Andersen SL, Arvanitogiannis A, Pliakas AM, et al.: Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Nat Neurosci 2002; 5:13-14.
Moll GH, Hause S, Ruther E, et al.: Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters. J Child Adolesc Psychopharmacol 2001; 11:15-24.
Zito JM, Safer DJ, dosReis S, et al.: Trends in the prescribing of psychotropic medications to preschoolers. JAMA 2000; 283(8):1025-1030.
For details on the PATS study, including eligibility requirements and contact information, please visit www.manisses.com/studies/studyinformation.
"Trigger Questions" to Assess Sleep History
The "BEARS" use a simple questionnaire to screen for the most common clinical sleep disorders
in children and adolescents ages two to 18 years. Divided into five major sleep domains,
the BEARS provides a set of developmentally appropriate "trigger" questions to be answered
by both the parent and child. Following are some example trigger questions:
Bedtime problems: Does your child have any problems at bedtime?
Excessive daytime sleepiness: Does your child have difficulty waking in the morning, seem sleepy during the day, or take naps?
Awakenings during the night: Does your child seem to wake up a lot at night? Any sleepwalking or nightmares?
Regularity and duration of sleep: What time does your child go to bed and get up on school days? Weekends? Do you think he/she is getting enough sleep?
Sleep-disordered breathing: Does your child have loud or nightly snoring or any breathing difficulties at night?
© Owens JA: Taking a sleep history -- the BEARS approach.
Most ADHD Boys at No Higher Risk for Delinquency
Tue Aug 27, 1:45 PM ET
By E. J. Mundell
CHICAGO (Reuters Health) - The majority of young boys with attention-deficit/hyperactivity disorder (ADHD) are no more likely to exhibit destructive, delinquent behavior as teenagers than children without the disorder, researchers report.
However, a minority of boys with ADHD and a co-existing pattern of aggressive behaviors may be at increased risk for delinquency in later life.
"The essential finding here is that ADHD in and of itself does not predict the severity or seriousness of delinquency in adolescence. It really is ADHD kids who are also aggressive who are at much more significant risk," said researcher Dr. Steven Lee of the University of California at Berkeley.
He presented the findings here earlier this week at the annual meeting of the American Psychological Association.
ADHD is characterized by impulsive behavior and difficulties in paying attention, as well as academic and behavioral problems. Up to 5% of school-age children are estimated to have ADHD, with boys diagnosed up to four times more often than girls.
Speaking with Reuters Health, Lee said that over the past 30 years, studies on the long-term behavioral outcomes of ADHD children have been "relatively inconsistent."
"The biggest problem," he said, "was the fact that anywhere between 35% and 50% of children with ADHD are also aggressive at the same time," exhibiting a pattern of behaviors such as physical or verbal assault against others, usually other children.
Beginning in the early 1990s, Lee and colleagues used a summer camp format to follow the 5-year development of 175 boys ranging from 6 to 12 years of age. One hundred of the boys were diagnosed with ADHD, while the remaining 75 showed no signs of the disorder.
Based on interviews with parents, camp counselors and the children themselves, they determined which boys also showed signs of aggressive behaviors.
By the end of the study the boys had grown to 11 to 18 years of age, "that ripe period for adolescent development and delinquency," according to Lee.
The investigators found that boys who had scored "in the highest (top 25%) level of aggression were 17 times more likely to be in the relatively more severe category of delinquency relative to the remaining 75% of the kids," Lee said.
The researchers' definition of "severe" delinquency included behaviors such as gang fighting, property damage or other violent acts.
On the other hand, boys diagnosed with ADHD but without high levels of aggression appeared to be "at no greater risk" of delinquency than typical kids, Lee said. "They are not aggressive and consequently they are not at risk for adolescent and adult antisocial behavior."
And even boys with ADHD plus aggression are not doomed to delinquency down the road, Lee added. "Even if you are in the top 1% of ADHD-aggression, there are successful interventions that show good effects over time," he said.
Studies show that both child- and parent-centered psychotherapies can be effective in changing antisocial behaviors in exactly these types of boys, according to the researcher. "Early intervention, in school, at home, in social relationships is really crucial for the children to develop successfully," Lee said.
He stressed that data on all of the children in the study were collected only when they were not on ADHD medications such as Ritalin ( news - web sites). While medication may help curb ADHD, evidence on its ability to prevent aggression is mixed, Lee noted. For aggressive boys, "only in very rare circumstances would medication alone be better than having medication in addition to psycho-social interventions," he said.
The Berkeley researchers are currently conducting a similar study focused on girls with ADHD.
New ADHD Drug Promising in Early Studies
NEW YORK (Reuters Health) - A new drug being developed as a treatment for attention deficit hyperactivity disorder (ADHD) in children may be an alternative to Ritalin, according to results presented at a meeting Thursday
In two trials, a total of 291 children with ADHD, between 7 to 13 years of age, received 9 weeks of treatment with either Ritalin, the new drug, called tomoxetine, or an inactive placebo. The results were presented at the American Academy of Child and Adolescent Psychiatry annual meeting here. Although tomoxetine fell just short of being as effective as Ritalin, the drug did reduce symptoms in most children, according to Eli Lilly, the company developing the drug.
Unlike Ritalin or Dexedrine, tomoxetine, is not considered a stimulant Tomoxetine is a very exciting option that could help people for whom stimulants don't help or they're not used for other reasons,'' Dr. Thomas Spencer of Massachusetts General Hospital, a scientist involved with the trials, told Reuters Health about 30% of kids don't respond to Ritalin but tomoxetine has a completely different mechanism
Eli Lilly researcher Dr. John Heiligenstein, speaking at the meeting, added that ``there is a clear advantage for non-stimulant drugs that come to the market. In addition, Dr. Spencer said, tomoxetine ``is very selective and has very few side effects.'' Due to their potential for abuse,
Ritalin and Dexedrine are classified as controlled substances. Adverse effects can include loss of appetite, anxiety, Hallucinations, changes in mood and insomnia.
In contrast, Lilly maintains that the only side effect associated with tomoxetine in the trials was loss of appetite. Tomoxetine also had less of an effect on sleep than Ritalin, the company noted.
The company is undertaking a larger study with 1,000 to 1,500 patients, Dr. Spencer noted the company anticipates completing that study early next year, a Lilly spokesperson told Reuters Health. Assuming a quick filing of a new drug application with the US Food and Drug Administration (FDA), tomoxetine could, if approved, be on the market as early as 2002``There is general agreement that it would be wonderful to have an alternative to the stimulants,'' Dr. Spencer said. Two other companies, Glaxo Wellcome and Abbott Laboratories, are also developing non-stimulant treatments for ADHD. Results of a study of Glaxo's experimental drug GW320659 were presented at the same meeting this week. The results showed that the drug was ``well tolerated and may be effective in treating ADHD in children,'' Glaxo spokesperson Holly Russell told Reuters Health.
Glaxo's drug is slightly different from tomoxetine, but it is still considered a non-stimulant, Russell said. She added that the company is not strictly focusing on ADHD but instead plans to develop GW320659 ``quite broadly in a range of therapeutic areas. Abbott Laboratories is developing another drug, called ABT089, which ``is very different than Ritalin,'' a company spokesperson told Reuters Health. ABT089 ``acts on different receptors in the brain (than Ritalin),'' the spokesperson said.ABT089 is still in laboratory studies and it remains uncertain when trials in humans may be launched, she said.
Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder
Spencer T, Biederman J, Wilens T, Prince J,Hatch M, Jones J, Harding M, Faraone SV, Seidman L
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114, USA.
Am J Psychiatry 1998 May; 155(5):693-5
OBJECTIVE: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). METHOD: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. RESULTS: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptom was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. CONCLUSIONS: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment.
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News from the AMA:
Pervasive Developmental Disorders Among Pre-School Children May Be More Common Than Previously Thought
English Survey Documents Rates of Autism and Related Disorders
June 26, 2001 — A survey of pre-school children in England suggests the prevalence of pervasive developmental disorders (autism and related disorders) is higher than previously reported, according to an article in the June 27 issue of The Journal of the American Medical Association.
Suniti Chakrabarti, M.D., M.R.C.P., of the Central Clinic in Stafford, England, and Eric Fombonne, M.D., F.R.C.Psych., of King's College in London, conducted a survey to estimate the prevalence of pervasive developmental disorders (PDDs) in a geographically defined population of pre-school children. Prevalence is the number of cases of a disease or disorder in existence at any one time in a defined population.
PDDs fall short of the strict diagnostic criteria for autism, and include several disorders and syndromes that are considered to be mental and/or behavioral disorders that may or may not have biological basis or causes. In this study, children were evaluated for PDDs that included autistic disorder (AD), Asperger syndrome (a condition in which children display autistic behavior, but have well-developed language skills), Rett syndrome (a disorder in which skills that have been acquired, such as walking and talking, gradually disappear; the child becomes progressively handicapped, and may appear autistic), childhood disintegrative disorder (a rare neurologic condition involving severe deterioration of mental and social functioning), and pervasive developmental disorder-not otherwise specified (PDD-NOS).
Autistic disorder (autism) is a severe developmental disorder involving abnormal and often delayed language development or communication skills, social interactions and reciprocity, and imagination, play and interests. According to background information cited in the article, rates of autism typically have been reported in the range of four to six per 10,000, although these figures increased in surveys conducted in the last 15 years.
The authors conducted their survey from July 1998 to June 1999 in Staffordshire, England. The area's 15,500 children aged 2.5 to 6.5 years were screened for developmental problems. Children with symptoms suggestive of a PDD were intensively assessed by a multidisciplinary team, which conducted standardized diagnostic interviews and administered pyschometric tests.
The researchers report that a total of 97 children (79.4 percent male) were confirmed to have a PDD. The prevalence of PDDs was estimated to be 62.6 per 10,000 children. The prevalence was 16.8 per 10,000 for autistic disorder and 45.8 per 10,000 for other PDDs.
"In our survey, AD accounted for only 27 percent of the cases, with these children showing much greater cognitive and language impairments," the authors write. "By contrast, the majority of cases was found at the mild end of the autistic spectrum, with the PDD-NOS and Asperger syndrome groups accounting for 71.1 percent of the cases. The inclusion of these milder variants certainly may account for a substantial part of the increase in prevalence rates."
The average age at diagnosis was 3 years, 5 months, and 81 percent of the children were originally referred by health visitors (nurse specialists). "Of the 97 children with a PDD, 25.8 percent had some degree of mental retardation and 9.3 percent had an associated medical condition," the authors report.
The authors point out that there appears to be a downward trend for the rate of mental retardation among children diagnosed with autism. "This shift has important implications for intervention, since the majority of these children will require education in mainstream schools with provision of individual support," they write. "In addition, it is possible that very early intervention in autism and PDD might be associated with a much better cognitive outcome in the short term."
Editor's Note: Funding for this study was provided by the First Community Health Trust.
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Editorial: Improving Early Detection Of Pervasive Developmental Disorders
In an accompanying editorial, Susan L. Hyman, M.D., and colleagues from the University of Rochester School of Medicine and Dentistry in Rochester, N.Y., emphasize the importance of determining the current prevalence of pervasive developmental disorders and of improving the early detection of affected children.
"There is increasing evidence that behavioral and educational intervention with young children may significantly improve developmental and behavioral outcomes and that basic deficits in play and communication may be therapeutically modified," they write.
They point to the study by Chakrabarti and Fombonne, corroborating that PDDs are not rare among pre-school children. "Given the limitations of current knowledge, valuable data sets such as these should be used to increase understanding of the characteristics of young children with PDD as well as to determine the current prevalence," they write. "Those figures will assist in planning for services that affected children and their families will need.
"Parent groups have allied with the U.S. Congress in a call for more research into the neurobiology, treatment, and epidemiology of these disorders," the editorialists conclude. "Although waiting for the answers that only careful research can give, it is incumbent on those who care for young children to identify the children with atypical social and language development, refer them for assessment, and advocate for effective treatments."
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Study Probes Dyslexia Troubles
Updated 6:35 PM ET February 15, 2001
By PAUL RECER, AP Science Writer
SAN FRANCISCO (AP) - Discovery of a deficit in key reading and visual centers of the brain could lead to early diagnosis and treatment for a disorder that affects about 15 percent of the population, researchers report.
A study at Georgetown University Medical Center in Washington suggests that people with dyslexia have a much lower level of activity in the brain's left inferior parietal, an area that is important both in reading and in processing of visual images.
Dr. Guinevere Eden and Dr. Thomas Zeffiro, a husband and wife team and co-directors of the Center for the Study of Learning at Georgetown, also found that the right inferior parietal can be taught to compensate for the weakness in the left side of the brain through a program of intense reading training.
"These study results are further evidence that dyslexia has biological roots," said Eden. She and Zeffiro discussed their study Thursday at the national meeting of the American Association for the Advancement of Science.
Dyslexia is generally diagnosed in elementary school children who have great difficulty learning to read. The core of this difficulty, said Eden, is the inability to link up visual symbols with sounds, an essential process in reading. A youngster with dyslexia, for instance, could not associate the sounds in the spoken word "cat" with the letters that make up the simple word, said Eden.
It is estimated that 5 percent to 15 percent of the population suffers from some degree of dyslexia, she said. Some learn to compensate and eventually become good readers, but Eden said many adults cannot read because the problem was not identified and treated during their school years.
In their study, Eden and Zeffiro used functional magnetic resonance imaging, a technique that, in effect, takes pictures of the brain while thinking processes are under way.the test involved reading and following the direction of moving dots on a screen.In the test, they compared 20 people with dyslexia with 17 without the disorder. Among those without the disorder, the left inferior parietal region was very active. But for those with dyslexia, there was significantly less activity. Eden said the findings are important because they suggest it might eventually be possible to develop a test that would identify dyslexic children at a very early age.
"Today we are able to diagnose dyslexia only after children have shown difficulty in learning to read, usually around the time they're in second or third grade," Zeffiro said in a statement. "If we know that the same areas of the brain used for reading are also used to perform other types of visual tasks, then we can test children before they reach reading age." Eden said it may be possible to perform such tests in children as young as four or five.
In another study, Eden said two groups of 10 adults, all with dyslexia, received MRI brain scans to establish their individual level of brain activity during reading and visual activities.
Then one group was put through an intensive, eight-week program of training in reading. The other group of 10 did not receive such training. At the end of the period, Eden said, all 20 adults were again given brain scans while performing reading and visual activities. The adults who had received the training showed increased activity in the right inferior parietal, while those without the training had no difference in the brain scan. "This shows that the brain, even in adults, is plastic, that it can be made to compensate," said Eden. She said it is a myth that the defining characteristic of dyslexics is the tendency to see letters reversed.
Virtually all children have this problem to some degree, but outgrow it, she said. The reversals were long considered a primary symptom of dyslexia simply because it takes much longer for dyslexics to overcome the problem, she said.
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A Controlled Clinical Trial of Bupropion for Attention Deficit Hyperactivity Disorder in Adults
Wilens TE, Spencer TJ, Biederman J, et al
Am J Psychiatry. 2001;158:282-288
Approximately one half of children with a diagnosis of attention deficit hyperactivity disorder (ADHD) progress to have symptoms of the disorder as an adult. Stimulant medications have been the first-line treatment for adult ADHD, but they have some drawbacks, such as potential for abuse, multiple daily dosing, and anxiogenic effects. The tricyclic antidepressants and buproprion are considered second-line treatments for children with ADHD. The authors examined the efficacy of buproprion in the treatment of ADHD in 40 adults with a diagnosis of ADHD in a double-blind, randomized, parallel study. Twenty-one patients were assigned to the buproprion group and 19 were given placebo. The patients receiving buproprion received dosages up to 200 mg twice daily. The authors discovered that at the end of 6 weeks, 76% of the buproprion group showed improvement in their symptoms compared with 37% in the placebo group. Side effects noted buproprion group included headache, gastrointestinal disturbance, insomnia, and aches or pains. No serious adverse effects were noted. The authors concluded that buproprion was an effective treatment choice for adults with ADHD, and could be considered a first-line choice for patients with comorbid substance abuse or mood/depression symptoms.
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