PEDIATRICS Vol. 118 No. 6 December 2006, pp. e1860-e1866 (doi:10.1542/peds.2005-3101)
ARTICLE |
Pervasive Developmental Disorder, Behavior Problems, and Psychotropic Drug Use in Children and Adolescents With Mental Retardation
a University Medical Center Groningen/Accare University Center for Child and Adolescent Psychiatry, Groningen, the Netherlands
b Department of Social Pharmacy, Pharmacoepidemiology, and Pharmacotherapy, Groningen University Institute of Drug Exploration, Groningen, the Netherlands
c Research Methodology Group, Social Sciences Wageningen University Research, Wageningen, the Netherlands
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
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OBJECTIVE. This study investigated the interrelationship between psychopharmacotherapy in general and the use of specific psychotropic drugs and pervasive developmental disorder and other behavior problems in children and adolescents with mental retardation.
METHODS. A total of 862 participants 4 to 18 years of age, including all levels of mental retardation, were recruited through facilities for children with mental retardation in Friesland, the Netherlands. Information on medication was collected through parent interviews. Behavior problems were investigated with a standardized parent questionnaire (Developmental Behavior Checklist). A pervasive developmental disorder classification was based on the Pervasive Developmental Disorder in Mental Retardation Scale, completed by psychologists or teachers. Logistic regression analysis was used to investigate the relationship between the use of psychotropic drugs and pervasive developmental disorder and other behavioral problems, in the presence of possible confounders.
RESULTS. One of 10 participants used psychotropic medication. The main factors associated with psychotropic drug use were pervasive developmental disorder and disruptive behavior. The level of functioning was also associated. Self-absorbed behavior was statistically significantly associated with clonidine use and disruptive behavior with stimulant use. Pervasive developmental disorder and communication problems were the main factors associated with the use of antipsychotic drugs. Age also played a role, whereas gender, living situation, and level of mental retardation did not.
CONCLUSIONS. Antipsychotic drugs were associated with pervasive developmental disorder, whereas clonidine and stimulants were associated with self-absorbed and disruptive behavior, respectively. Although clonidine and risperidone are not registered for the problems reported and the other nonstimulants were only sometimes used on-label, their use was associated with specific psychiatric or behavioral problems.
Key Words: mental retardation • children • adolescents • psychopharmacology • pervasive developmental disorder • behavior problems • psychotropic agents
Abbreviations: MR—mental retardation • PDD—pervasive developmental disorder • DBC—Developmental Behavior Checklist • PDD-MRS—Pervasive Developmental Disorder in Mental Retardation Scale • OR—odds ratio • CI—confidence interval
Few studies of psychotropic drug use among children and adolescents with mental retardation (MR) have been conducted.1,2 Such studies are needed, because many problems are encountered when psychotropic drugs are prescribed for this vulnerable group. For example, Aman et al3 noted a lack of empirical data for the pharmacologic treatment of most disorders in children and adolescents with MR. In addition, the practice parameters for the assessment and treatment of children, adolescents, and adults with MR and comorbid mental disorders published by the American Academy for Child and Adolescent Psychiatry4 summarize several problems that are encountered frequently, including irrational prescribing, medication that does not seem to be part of a comprehensive treatment plan, medication that may not be appropriate for the diagnosis, inadequate dosage, and questionable monitoring of adverse effects. Because of these problems, the practice parameters indicate that psychotropic medications should be prescribed very carefully for individuals with MR, and this seems to be even more important for children. Therefore, studies of the psychopharmacologic treatment of a population of children and adolescents with MR are needed to increase the insight into the prevalence, the classes of drugs prescribed, and the related factors (such as behavior problems or disorders).
To date, most conducted studies have focused on specific subpopulations within the population with MR, such as institutionalized individuals,5–7 individuals receiving services from an outpatient, community-based, mental health/MR authority,8 individuals from a dual-diagnosis treatment unit in a clinic,9 or specific diagnostic groups (eg, autism10) (see the report by Matson et al11 for a review). Singh et al6 pointed out that, in many studies, psychotropic medication use was not reported separately for children or adolescents and adults. Recently, Tobi et al12 reported specifically on a population of children and adolescents with MR. They found high rates of off-label prescription and chronic medication use in general, including use of psychotropic drugs, such as 28% off-label prescription use of nervous system drugs, much higher than the 20% unaccepted use reported for adults with MR.8 Although this does not necessarily mean prescribing without any safety or efficacy information, it is important to be aware of this relatively high rate of off-label psychotropic drug use in this vulnerable population.
A specific subgroup within the population with MR that is known to be medicated frequently10,11 is the group of individuals with pervasive developmental disorder (PDD). PDD is defined as "severe and pervasive impairment in several areas of development: reciprocal social interaction skills, communication skills or the presence of stereotyped behavior, interests and activities."2 Autistic disorder is known as the core disorder in the spectrum of PDD. The prevalence of PDD in children and adolescents with MR has been estimated recently at 16.7%.13 Children with MR and PDD often show 3 types of problems.5,14–17 In addition to the specific PDD problems (the core problems of the disorder), children and adolescents with MR and PDD suffer from severe semispecific and nonspecific problems.5 Semispecific problems stem from the specific PDD problems, resulting in rigidity, stereotyped behavior, self-injurious behavior, and fears. These problems are less specific for PDD but occur more often in individuals with MR and PDD than in those without PDD. Nonspecific behavior problems, such as aggression, temper tantrums, and hyperactivity, can also be present. Although these problems are not specific for or more frequent in individuals with MR and PDD, they affect the development and life of a child severely when they are present. Specific problems are inevitable, because of the nature of the disorder. However, semispecific or nonspecific problems are more or less indirect consequences of the disorder and may, with the right treatment, be decreased or prevented. Medication may be used as part of such treatment, as indicated by Langworthy-Lam et al,10 who reported that 45.7% of their study subjects with MR and autism used psychotropic drugs (in almost one half of cases, >1 type). As described by Matson et al11 in their review of psychopharmacologic treatment and MR, antipsychotic drugs were the most frequently used drugs when autism was present. However, antipsychotic drugs almost never were prescribed for the autistic symptoms themselves (the specific problems) but almost always were aimed at the semispecific and nonspecific problems. The current study aimed to investigate the prevalence of psychotropic drug use in children and adolescents with MR and to examine possible factors related to the use of specific classes of psychotropic drugs, specifically focusing on the presence of PDD and other semispecific and nonspecific behavior problems.
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METHODS |
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Participants
The present study was part of a large epidemiologic study into behavior problems, health problems, medication use, and other concerns in children and adolescents with MR. The participants were recruited through facilities for children and adolescents with MR (schools, day care facilities, and institutions) in Friesland, a northern province of the Netherlands. In the Netherlands, all children known to have MR are known to one or more of these facilities, regardless of their health insurance. No participants were excluded on the basis of the cause of MR, the presence of sensory or motor impairments, or comorbid psychiatric disorder or behavioral problems. All levels of MR were included.
The level of functioning was classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision,2 as borderline intellectual functioning (IQ of 70–85), mild MR (IQ of 50–70), moderate MR (IQ of 35–55), severe MR (IQ of 20–40), or profound MR (IQ of <20). Participants were classified into a category on the basis of their performance on standardized tests, as described previously.13 Participants were regarded as institutionalized when they lived away from home >4 days per week. The procedures were described in more detail elsewhere.13,18 For the present study, 862 participants were included, 4 through 18 years of age, with available parental information on medication use and behavior problems and a Pervasive Developmental Disorder in Mental Retardation Scale (PDD-MRS) classification. All information was collected after informed consent was obtained from parents.
Instruments
Information on psychotropic drug use was collected through a comprehensive parent interview, which also included demographic items, background questions on the physical and mental health of the child and other family members, the burden on the family, and adaptive functioning.19,20 Data collection took place from the summer of 1998 through the summer of 2000. Additional information from medical records was not available. The brand or generic drug names mentioned by parents were classified according to the World Health Organization Anatomic Therapeutic Classification system.21 For drugs that possibly could be classified in several categories, the purpose of the pharmacotherapy, according to the parents, was used to determine the Anatomic Therapeutic Classification category. Psychotropic drugs were defined as medications for the nervous system, excluding analgesic and antiepileptic drugs. Therefore, the evaluated drugs included clonidine, anti-Parkinson disease drugs, antipsychotic drugs, anxiolytic drugs, hypnotic/sedative drugs, antidepressants, and stimulants.
The presence of PDD was assessed with the PDD-MRS.18,22,23 The PDD-MRS is an originally Dutch instrument for the PDD spectrum that is based on the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, including autistic disorder and PDD not otherwise specified but with no differentiation between them. It is well studied and has been widely used since 1990 in the care of people with MR in the Netherlands and Belgium.5 The instrument was developed for use with children and adults with MR. It contains 12 dichotomous items on the 3 aspects of PDD (communication, social behavior, and stereotyped behavior), to be completed by clinicians after direct observation. Weighted factors of 1, 2, or 3 are assigned to the item scores, and the maximal score is 19. Psychometric qualities were tested in a large population (N = 1230), including all levels of MR. Sensitivity (92.3%) and specificity (92.4%) were excellent, compared with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis made by a clinician. Scores on the PDD-MRS are divided into 3 categories, namely, a PDD category (scores of 
10), a doubtful PDD/non-PDD category (scores between 7 and 9), and a non-PDD category (scores of 
6). In this study, school psychologists or teachers completed the PDD-MRS. The PDD-MRS classifications were used to investigate the relationship between psychotropic drug use and PDD.
Behavior problems were investigated with the Developmental Behavior Checklist (DBC),24–26 which was designed specifically for assessing emotional and behavior problems in children with MR, with 5 empirically derived subscales, that is, disruptive/antisocial (27 items), self-absorbed (31 items), communication disturbance (13 items), anxiety (9 items), and social relating (10 items). Parents reported whether the 96 items were applicable to their child "clearly or often" (score of 2), "a little or sometimes" (score of 1), or "not applicable at all" (score of 0) over the past 6 months. Reliability and validity were studied in Australian and Dutch populations and were found to be good.24,26 The DBC contains items on PDD spectrum behaviors, but none of the subscales is a specific PDD subscale. The scores on the subscales were used to measure the relationship between psychotropic drug use and behavior problems other than PDD.
Statistical Analyses
Student's t test, 
2 test, and analysis of variance were conducted to assess bivariate associations between demographic and clinical variables. The relationship between the use of general and specific psychotropic drugs and behavioral problems and PDD, in the presence of other possible factors, was investigated with logistic regression analysis (SPSS 12.0; SPSS, Chicago, IL). All fitted models included the variables of DBC subscales, PDD-MRS classifications, levels of MR, living situation (at home or not), gender, and age. The odds ratios (ORs) for any variable in the analysis express the relationship with an increase or decrease in the odds of using a specific class of psychotropic drugs. A P value of .05 was considered significant. All analyses were conducted twice, once for the total group and once for the group without the children who used the drug in question in combination with another psychotropic drug. The tables show results for the total group, and possible differences from those results for the "single-use" groups are mentioned in the text.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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The characteristics of the sample are presented in Table 1. Children with profound MR lived away from home more often; children in the 2 lower levels of MR were classified as having PDD more often, and their DBC scores were higher than those of children in the higher levels of functioning.
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In the total sample, 83 children (9.6%) used psychotropic drugs, 10 of whom used >1 type. The prevalence of psychotropic drug use ranged from 8.7% in the moderate and mild levels to 17.0% in the borderline level of functioning, with no statistically significant differences between the various levels of MR.
The results of a logistic regression analysis of psychotropic drug use that included PDD, other behavior problems, and possible confounders (level of MR, age, gender, and living situation) are presented in Table 2. As shown, PDD classification on the PDD-MRS and disruptive behavior problems on the DBC were associated with psychotropic drug use, after controlling for a list of confounders. The OR of 2.61 for PDD means that a child with PDD on the PDD-MRS would have a 2.61 times higher odds or probability of using psychotropic medication than a child without PDD on the PDD-MRS. For the DBC, any additional 1 point on the disruptive scale increased the odds of psychotropic drug use by a factor 1.05. In other words, each extra 1 point in the score of the disruptive subscale increased the probability that a child would use psychotropic medication by 5%. Of the confounders, gender, age, and living situation did not play a role. Children with profound MR had significantly lower odds of using psychotropic medication, compared with children with borderline MR. Exclusion of the 10 children using multiple psychotropic drugs from the analyses did not affect these outcomes.
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Because psychotropic medication consists of various classes of drugs, all with specific mechanisms and all presumably prescribed for specific problems, it was of clinical interest to see how the factors described above were related to the use of specific classes of psychotropic drugs. Therefore, logistic regression analyses were conducted for 3 specific psychotropic medication classes, namely, clonidine, stimulants, and antipsychotic agents (Table 3). The prevalence of use of the other types of psychotropic medication was too low to be analyzed in more detail (anti-Parkinson disease drugs for 2 children, anxiolytic drugs for 6, hypnotic/sedative drugs for 3, and antidepressants for 2).
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The odds of using stimulants (used by 2.3% of the studied sample) were increased only by disruptive behavior problems, as measured with the DBC, with a factor of 1.08, or 8%, for each additional 1 point on this subscale. Excluding the 3 children who used other drugs with stimulants did not affect the outcomes. With respect to clonidine (2.9%), each extra 1 point on the self-absorbed subscale of the DBC increased the probability of use with a factor of 1.08, or 8%. Without the 5 children who used clonidine with another psychotropic drug in the analysis, the results changed from self-absorbed to disruptive, increasing the odds with a factor of 1.07 (7%) for each additional 1 point on this subscale of the DBC in the single-use group (95% confidence interval [CI]: 1.00–1.13; Wald statistic: 4.43). Neither PDD nor any of the other factors was related to the odds of clonidine or stimulant use.
Concerning antipsychotic drugs (3.9%), PDD and communication problems on the DBC increased the odds of use. A child with PDD on the PDD-MRS was 5.6 times more likely to use antipsychotic drugs than a child without PDD. In addition, each extra 1 point on the DBC communication subscale increased the probability of using antipsychotic drugs by 12%. Of the confounders, living away from home increased the odds of antipsychotic drug use 2.57-fold. Age and antipsychotic drug use also were related; older children and adolescents more often used antipsychotic drugs. Exclusion of the 9 children who used antipsychotic drugs with another psychotropic drug from the analysis did not affect the outcomes greatly; the only change was that living away from home no longer statistically significantly affected the odds.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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The aim of this study was to investigate psychotropic drug use in a population of children and adolescents with MR, in relation to PDD and other behavior problems. Psychotropic drugs were defined as medication for the nervous system, excluding analgesic and antiepileptic drugs.
Compared with children from the general Dutch population 0 to 19 years of age (data from 1999),27 children with MR used psychotropic drugs approximately twice as often. Because psychiatric and behavior problems are known to be more prevalent in children and adolescents with MR, compared with the general population,28,29 this may be easily understood. The current study indicates that nearly 1 in 10 children and adolescents with MR uses psychotropic medication. This is a lower prevalence than the prevalence reported by Singh et al6 in their review of psychopharmacoepidemiologic features in MR (published in 1997 and based on studies from 1986–1995), which may be explained by differences between the populations studied. Singh et al6 reported prevalences of 19% to 29% for children and adults together and 11% for a school population. Our study included only children but also those with lower levels of functioning, who were unable to attend school.
Several factors were associated with psychotropic drug use in children with MR. Children with PDD were more than twice as likely to use psychotropic drugs, and disruptive behavior problems also played a major role. This seems to indicate that psychotropic drugs were prescribed specifically for additional disabling psychiatric symptoms or behavior problems, apart from MR. Children with a profound level of MR were less likely to use psychotropic medication than were children from the borderline level of functioning. This may be explained by the complex clinical picture that these children often present to professionals, with many other problems such as somatic problems or epilepsy. With these problems in the foreground and a usually restricted behavioral repertoire, behavior problems may not represent a reason to prescribe psychotropic medication. In addition, reliance on parents to report the use of medication by their child might have resulted in underreporting of psychotropic drug use for institutionalized children, who are most frequently in the profound level of MR.
Three kinds of psychotropic drugs (clonidine, antipsychotic drugs, and stimulants) were investigated more thoroughly. Compared with the general Dutch population 0 to 19 years of age,27 children with MR used stimulants 3 times more often (MR: 2.3%; general: 0.74%), clonidine 9 times more often (MR: 2.9%; general: 0.31%), and antipsychotic drugs 11 times more often (MR: 3.9%; general: 0.34%). It should be noted that a broader definition was used (1 prescription in a pharmacy database) for the prevalence in the general population; therefore, the presented differences are likely underestimated.
In the present study, clonidine seemed to be prescribed for self-absorbed behavior problems or, with exclusion of the multiple-drug users, for disruptive behavior problems. In all cases of multiple-drug use among the clonidine users, the additional medication was an antipsychotic agent. Therefore, this can be assumed to be a group with very complicated behavior. Combining clonidine and antipsychotic drugs seems to be an effective treatment for disruptive behavior problems in this subgroup, because these problems were noted as salient only when the multiple-drug users were excluded from the analysis. Stimulant use was associated with disruptive behavior problems. The use of antipsychotic drugs was related to PDD and communication problems, a DBC subscale that reflects many PDD-related problems (such as echolalia, tone of voice, no interaction with peers, and restricted interests). This corroborates the conclusions of Matson et al,11 in their review of psychopharmacologic treatment in MR, that antipsychotic drugs were used most frequently for autism or PDD. Other studies indicated good effects of antipsychotic drugs in PDD,30–32 and prescribing antipsychotic drugs when this disorder is present seems to have a rationale. For children with MR and PDD, however, studies are needed to investigate the effects of antipsychotic drugs in relation to the risks in this vulnerable group.
Some limitations should be kept in mind when the results are interpreted. First, the information on medication use was given by parents and was not collected from medical records. With this method of data collection, comparisons with other studies may be complicated. In addition, the most dramatic increase in psychotropic drug use in the general pediatric population took place before the year 2000.27,33 With the assumption that this trend was similar in the population of youths with MR, the present study might underestimate slightly the current use of stimulants in this population. Another limitation concerns the representativeness of the sample. Higher levels of functioning seem to be slightly underrepresented, whereas lower levels seem to be overrepresented, compared with the total population of children and adolescents with MR in Friesland.13 Furthermore, children and adolescents with a borderline IQ level in the present study cannot be regarded as representative of children and adolescents with a borderline IQ level in general, because the population under study received special education or used facilities serving children and adolescents with MR. The fact that they were approached through these facilities suggests that they were unable to function in normal education, which might be related to specific physical, health, or behavior problems.
Even with these limitations in mind, we can conclude that the prevalence of psychotropic drug use is high for children with MR. Additional, disabling, PDD-related problems are the most predictive of the use of antipsychotic drugs. Self-absorbed and disruptive behavior problems are associated with the use of clonidine and stimulants, respectively. This indicates clearly that clinicians are using these medications to target symptoms that are not captured in the diagnosis of MR. Whether a drug is used off-label depends on the particular compound, the age of the child, and the indication/reason for prescribing. Most of the psychotropic drugs in this study were not registered for the problems reported in these children (except for methylphenidates), and clonidine was always off-label. For the antipsychotic drugs, the status depended on the particular compound; risperidone was off-label but pimozide was sometimes on-label.12 Although clonidine and risperidone were used off-label, their use was associated with specific behavior problems. Additional research is needed to balance the benefits of a more-functional life for children and adolescents with MR with the risks of psychotropic medications in this vulnerable group.
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ACKNOWLEDGMENTS |
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We thank the Netherlands Organisation for Scientific Research and the Korczak Foundation for Autism Research for financial support for this study.
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FOOTNOTES |
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Accepted Jun 19, 2006.
Address correspondence to Annelies de Bildt, PhD, University Medical Center Groningen/Accare, University Center for Child and Adolescent Psychiatry, PO Box 660, 9700 AR Groningen, Netherlands. E-mail: a.de.bildt{at}accare.nl
The authors have indicated they have no financial relationships relevant to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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