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Professional Psychology: Research and Practice Copyright 2002 by the American Psychological Association, Inc.
Pediatric Psychopharmacology: A Review of New Developments and Advances in psychopharmacology have revolutionalized the management of emotional and behavioraldisorders in children and adolescents. Recent developments in pediatric psychopharmacology and theprevalence of pharmacotherapy for various psychological disorders in children are examined, and clinicalupdates for classes of psychotropics are provided. Issues including monitoring and assessing drug effects,acceptability and satisfaction, and the social, political, and cultural issues surrounding the use ofpsychotropics in children are discussed. The authors conclude that the current clinical use of psycho-tropics in children exceeds extant efficacy and safety data. The involvement of practicing psychologistsin pediatric psychopharmacology and the need for a firm empirical foundation for pediatric psycho-pharmacology are also discussed.
Nearly every practicing psychologist who has worked with effects of these medications (Barkley, McMurray, Edelbrock, & pediatric populations has encountered a patient who is receiving Robbins, 1990; Drotar, 1995; Stancin, 1999).
psychotropic medication. A systematic effort to contain and drive In this article, we argue that the clinical use of most psycho- down the costs of medical care has dramatically changed health tropic medications far exceeds the data available regarding their care services in this country (Brown & Freeman, in press). Cost- safety and efficacy. We surveyed major research programs in an containment efforts have emphasized limiting referrals to specialty attempt to provide the major developments in both basic research providers and using designated points of service within the pri- and clinical use of psychotropics. Due to limitations in the space mary care system (American Academy of Pediatrics, 2000). The provided, the literature reviewed here does not represent an ex- result has been the decrease in the availability of mental health haustive review of pediatric psychopharmacology. Rather, the services for children and placements of limits on psychotherapy purpose of this article is to illustrate the available empirical data and specialized mental health services. Because primary care pe- supporting the efficacy and safety of various psychotropic agents.
diatricians have also become increasingly involved in gatekeeping, For a complete review, the reader is referred to several compre- accessing, coordinating, and even providing for mental health hensive sources on pediatric psychopharmacology (e.g., Brown & services, it is no surprise that primary care providers (e.g., pedia- Sawyer, 1998; Phelps, Brown, & Power, 2001; Werry & Aman, tricians, family care providers) prescribe the majority of psycho- 1999). For other pharmacotherapies in children and adolescents tropic medications for children (De Leon & Wiggins, 1996). One including the pharmacological management of pain, the reader is offshoot of this state of affairs has been an increase in opportuni- referred to Dahlquist (1999), Tarnowski and Brown (1995), and ties for practicing psychologists who work with children to enter Tarnowski, Brown, Dingle, and Dreelin (1998). Although we do into productive and collaborative relationships with pediatricians, not provide an exhaustive review of the literature, we do hope that both to identify types of psychopathology or learning disorders this article will broaden practicing psychologists’ critical thinking that may respond to psychotropic medication and to quantifiably about the use of major psychotropics in pediatric populations and assess the response to psychotropic agents and the possible adverse stimulate issues pertaining to research and training in pediatricpsychopharmacology.
RONALD T. BROWN received his PhD in 1978 from Georgia State Univer- Practicing Psychology and Pediatric Psychopharmacology sity. He is a professor of pediatrics and health professions and an associatedean in the College of Health Professions at the Medical University Advances in neuroradiological and electrophysiological assess- of South Carolina. He is also editor-elect of the Journal of Pediatric ment techniques, coupled with greater understanding of the roles of neurotransmitters and structural differences in the brains of MORGAN T. SAMMONS received his PhD in 1989 from Arizona State children with learning disorders and various psychopathologies, University. He is a prescribing psychologist and head of the Mental Health have permitted a more complete understanding of the psychobiol- Department at the Naval Medical Clinic, Annapolis, MD.
ogy of learning disorders and other mental problems (for reviews, OPINIONS EXPRESSED BY MORGAN T. SAMMONS do not relect official policies see Brown & Donegan, 1995; Brown & Sawyer, 1998; Phelps, or opinions of the U.S. Navy or the Department of Defense.
Brown, & Power, 2001). The body of knowledge in neural phys- CORRESPONDENCE CONCERNING THIS ARTICLE should be addressed to Ronald iology parallels new developments in psychopharmacology and T. Brown, Department of Pediatrics, Medical University of South Caro-lina, 19 Hagood Avenue, Suite 910, Charleston, South Carolina 29425.
has led to the introduction of a large number of pharmacotherapies that are specific to cognitive processes, learning, and psychopa- thology (for reviews, see Brown & Sawyer, 1998; Phelps et al., consultation with pediatricians seems a natural next step for psy- 2001). Although advances in neurosciences are undoubtedly re- chologists who practice with children to take.
sponsible in part for the dramatic recent increase in the use ofpsychotropic medications for pediatric populations, particularly in A Rationale for Separating Adult and Pediatric the primary care setting (Zito et al., 2000), other more controver- sial reasons exist. As Kutcher (2000) observed, in many instancesclinical use has outstripped scientifically based study of these Phelps et al. (2001) provided a description of the many roles that drugs. The issue of overprescription of psychotropics in pediatric practicing psychologists may serve in making medication deci- populations, especially for those agents lacking rigorous evidence sions, evaluating treatment effectiveness, and maintaining family supporting their effectiveness and safety, has achieved preemi- involvement in the change process. These roles for psychologists nence in the field of pediatric psychopharmacology. Readers seek- include assessing emotional and behavioral problems that may beappropriate for pharmacotherapy; identifying intervention goals; ing clinical guidance from the pharmacological information pre- selecting empirically supported psychological interventions to ac- sented in this article would do well to interpret this information in company pharmacotherapy; and assessing therapy, readiness for light of this as yet unsettled and highly contentious issue.
change, and the social validity of medication effects. Specific roles There appears to be a natural affinity between the practice of for practicing psychologists in the medication process include psychology and pediatric psychopharmacology. This explains the designing medication-monitoring protocols, interpreting the re- significant contributions that practicing child psychologists have sults of medication-monitoring protocols, and coordinating the made to research endeavors in pediatric psychopharmacology.
Psychologists’ training in assessment and measurement has re- A number of factors other than age separate the practice of sulted in an armamentarium of measures for carefully monitoring psychopharmacology with children from that with adults. These medication effects (including actual response to medication within issues include physiological factors, psychological factors, and the realm of behavior and learning) as well as quantifying adverse Children and adolescents (unlike their adult counterparts) rarely initiate their own referral for behavioral and learning problems.
Younger children especially may have little influence on whether The rate at which medications are absorbed, distributed in the they receive psychotropic medications. This state of affairs places body, and metabolized by children differ markedly from adults greater responsibility on physicians for accurately identifying (Paxton & Dragunow, 1993; Werry & Aman, 1999). Great care those children who may appropriately respond to medication, to must be taken when deciding on particular medications or doses expose them to the fewest adverse effects, and to protect them for children, and changes in doses require consultation with the from being disadvantaged in other ways by medication effects practitioner who is familiar with physiological functioning in (Brown & Sawyer, 1998; Phelps et al., 2001). As Gadow, Nolan, children. When considering additional medications, the practi- Paolicelli, and Sprafkin (1991) observed, contacts between physi- tioner must take care to consider any adverse medication interac- cians and classroom teachers and the use of well-validated instru- tions that may occur from polypharmacy (the use of more than one ments often occur sporadically and infrequently. Pediatricians psychotropic simultaneously), an increasingly common practice in often rely on reports from caregivers who have little opportunity to observe children’s behavior at school. Thus, they may be unawareof the adverse effects of psychotropic medication on children’s learning, behavior, or peer relationships. In these endeavors, psy- Because young children do not have the cognitive schema from chologists skilled in both assessment of developmental and learn- which to describe accurately the physiological or psychological ing disorders as well as in psychological measurement have made changes that may be associated with the use of psychotropic important clinical and research contributions to the field of pedi- medications (for reviews, see Brown & Sawyer, 1998; Zametkin & atrics, particularly in the primary care setting (Stancin, 1999). As Yamada, 1999), the possible adverse events that may be associated Brown and Sawyer observed, practicing child psychologists and with these therapies, or the time course related to these changes, pediatricians may collaborate productively in determining whether obtaining information from other informants is imperative. Be- trials of psychotropic medication are appropriate, effective, and cause the level of agreement among child, parent, and teacher successful and also whether one particular dose is more effective reports of behavior is relatively poor (Achenbach, McConaughy, than another in unstructured versus structured activities. Such & Howell, 1987), the practitioner assessing medication response or collaboration requires that both professionals engage in systematic adverse effects must be skilled in obtaining information across data collection, guided by a reliable assessment process, to ensure a comprehensive, cost-effective evaluation. Given the interestamong both pediatricians and psychologists in evidenced-based medicine and empirically validated treatments, it is anticipated thatthis collaboration among the two disciplines will significantly Adherence to prescribed psychotropic management is a major enhance treatment decisions as well as document the efficacy of factor influencing efficacy of treatment. Unlike adults, children do particular psychotropic agents. Expanding their scope of practice not arrange their own appointments for treatment, and because to include psychopharmacology (American Psychological Associ- children may be reluctant to use psychotropic medication, pre- ation, 1996; De Leon & Wiggins, 1996) and pharmacological scribing medication for children is more complicated than for SPECIAL SECTION: PEDIATRIC PSYCHOPHARMACOLOGY adults. Because caregivers typically take responsibility for admin- affluent homes. Other epidemiological studies, however, have istration of children’s medication, parental attitudes invariably reported disparate rates of stimulant prescription among Hispanic influence children’s use of medication. Caregivers may be ambiv- or African American youth as compared with their Caucasian alent about using psychotropic medication, particularly when counterparts, with minority children being less likely to receive school staff initiates the referral and when the child’s behavior is such treatment (Fox, Foster, & Zito, 2000; Zito, Safer, dos Reis, & not deemed to be a problem at home. It is thus incumbent on practitioners to be skilled in dealing with pharmacological issueswith both children and parents.
In a relatively recent investigation, Aman, VanBourgodien, Coordination With Other Treatment Programs Wolford, and Saphire (1995) conducted a survey of members of Psychotropic medication in children is only one component in the Autism Society of North Carolina; drug information was the overall treatment program for children and adolescents. Psy- gathered for 838 individuals who ranged in age from infancy to chotropic medications for children are used to reduce symptom- adulthood. Findings revealed that nearly one third of the sample atology so that children are amenable to treatment in other settings, was receiving psychotropic medication, with the most common such as family psychotherapy and special education classrooms.
being antipsychotics (12%) or stimulants (7%).
Hence, the provider must not only monitor efficacy and safety ofpsychotropic medications but also coordinate other treatment pro- grams along with drug therapy. Finally, efficacy and adverse Compared with other psychiatric disorders in children and ad- effects associated with medication must also be assessed across olescents, there is a dearth of treatment studies related to the pharmacological management of depression in children. Earlierinvestigators (Keller, Lavori, & Beardslee, Wunder, & Ryan, Prevalence of Pharmacotherapy in Pediatric Populations 1991; Kovacs et al., 1984) reported low rates of pharmacotherapycompared with psychological interventions for depression in chil- No national database exists that provides comprehensive infor- dren. More recent investigators (Emslie, Mayes, & Hughes, 2000; mation regarding the number of children receiving specific phar- Martin, Kaufman, & Charney, 2000) have noted that the use of macotherapies for particular disorders (Gadow, 1999). Surveys of antidepressants in pediatric populations has increased significantly Medicaid and insurance company databases, however, suggest in the recent past, in spite of the small number of randomized increased use of psychotropics in pediatric populations (Vitiello, controlled trials supporting their use.
2001). Those disorders that have accounted for the majority ofpsychopharmacology prevalence studies include attention deficithyperactivity disorder (ADHD), mental retardation and develop- mental disabilities, seizure disorders, autism spectrum disorders, Although it has been estimated that 10% of school children mood disorders, enuresis, and Tourette’s syndrome.
between 5 and 16 years of age wet their beds (Mellon & McGrath,2000), one investigation has reported that only 2% receive some Attention Deficit Hyperactivity Disorder type of pharmacotherapy for enuresis (Foxman, Valdex, & Brook,1986). The primary pharmacotherapies that have been reported are For the past 3 decades there has been continued interest in the tricyclic antidepressants or the antidiuretic hormone desmo- determining whether psychotropic medications were overused or pressin (Dulcan, Bregman, Weller, & Weller, 1998). Pharmaco- prescribed capriciously for children with ADHD— or possibly therapy for enuresis may be somewhat effective in the short-term, even used as a substitute for school reform (Gadow, 1999). Safer but relapse rates are very high once medication is discontinued and Krager (1988) conducted studies of the prevalence of medi- (Glazener & Evans, 2000). Therefore, behavioral methods are the cation use for ADHD in schools in Baltimore County, Maryland.
preferred treatment for this childhood disorder.
Findings revealed that prevalence had doubled every 4 –7 yearsand that by 1987, 6% of the school population was receiving medication for the management of ADHD, with the highest prev-alence during the third grade. Rates were higher for public than for In the past, haloperidol has been the mainstay of treatment for private schools. Stimulant medications constituted 99% of pre- Tourette’s disorder, though discontinuation rates due to adverse scriptions, and boys were five times more likely than girls to side effects of this drug have been high (Robertson & Stern, 2000; receive medication. Safer, Zito, and Fine (1996) reported a 2.5- Stefl, Bornstein, & Hammond, 1987). More recently, the atypical fold increase in the number of children receiving stimulant drug antipsychotics such as olanzapine or ziprasidone have been inves- treatment, attributed in part to children being managed on stimu- tigated. Studies in which these agents are used generally find that lant medication for longer periods of time, a greater frequency of they are better tolerated than older drugs such as pimozide (cf.
children with learning disabilities and ADHD (primarily inatten- Onofry, Paci, D’Andreamatteo, & Toma, 2000; Parraga & Parraga, tive type) receiving stimulant drug therapy, a larger number of 2001). A small (N ϭ 28) placebo-controlled trial supporting the girls receiving stimulant medication, and the prescribing of stim- use of ziprasidone has been published (Sallee et al., 2000). In spite ulant medication during the summer months. Contrary to popular of the fact that most studies with newer agents are open-label, lore, children from low socioeconomic backgrounds were no more uncontrolled trials with small sample sizes and are thus inconclu- likely to receive stimulant medication than their peers from more sive, Robertson and Stern (2000) found sufficient evidence to recommend that haloperidol no longer be considered a first-line Few studies have examined the long-term clinical effects of the stimulants, including their safety and efficacy, although the recentclinical trial conducted by the National Institute of Mental Health(Multimodal Treatment Study for Children With ADHD Cooper- Mental Retardation Comorbid With Behavior Disorders ative Group [MTA], 1999) has provided important data that sug- Surveys of pharmacotherapy in institutions serving individuals gest the efficacy and safety for a controlled trial over the course of with either severe or profound mental retardation have revealed 14 months. Hinshaw (2000) has recommended that additional that 30 – 60% of residents have been managed with either stimu- research be undertaken, particularly those studies that examine the lants or antipsychotic drugs. Litigation regarding the maltreatment approach of combining stimulant medication with other behavioral of institutionalized patients has resulted in a number of studies indicating that many institutionalized individuals who are mentally Adverse effects of stimulant medications are classified as either retarded may be managed with behavioral approaches instead of short- or long-term. The magnitude of adverse effects of the medication (Aman & Singh, 1988; Hill, Balow, & Bruininks, stimulants has been associated with dose of medication; adverse 1985). Gadow (1999) has cautioned that there is little use of effects generally increase linearly with increased doses. Adverse standardized instruments to assess response to medication or to effects reported with both low and high doses include decreased quantify adverse side effects in children in either institutional or appetite, insomnia, anxiety, irritability, abdominal pains, and head- aches (Barkley, McMurray, Edelbrock, & Robbins, 1990). Otheradverse effects have included mood disturbances, tics, anxiety,nightmares, and social withdrawal (DuPaul, Barkley, & Connor, 1998). These adverse effects typically dissipate following cessa-tion of the medication.
Here we review the various classes of psychotropic agents that It has been estimated that less than 1% of children receiving have been used with pediatric populations. Specifically, we review stimulant medication develop abnormal movements or tics, and stimulants, antidepressants and mood stabilizers, antipsychotics, this requires that stimulant medication be administered judiciously anxiolytics, and sedatives. We also provide recent information for children with a family history of Tourette’s syndrome or regarding some of the newer approaches used in pediatric psycho- another tic disorder. More recently, there has been compelling pharmacology to manage behavioral and mood disorders and the evidence presented by Gadow (1997) suggesting that stimulants may be used safely for children with comorbid tic disorders. Untiladditional data are forthcoming, the judicious use of this class of medication is advised for children predisposed to a tic disorder.
Another frequent adverse event of stimulant medication is behav- Stimulant medications for children have been the most meticu- ioral rebound, or the deterioration of behavior to a level worse than lously researched and used medication in child mental health, baseline. Behavioral rebound is typically managed by adjusting the particularly for the management of ADHD (Bennett, Brown, dose of medication and imposing structure during this particular Craver, & Anderson, 1999; Phelps et al., 2001). The use of period of the day, as well as increasing the use of behavior stimulants has increased dramatically over the past several years management techniques as the beneficial effects of the stimulant (Safer & Krager, 1988) and there has been a significant increase in the use of stimulants for preschoolers (Rappley et al., 1999; Zito et There has been some concern that stimulants may decrease al., 2000). Although stimulant drug therapy is not a panacea and prosocial behaviors (Jacobvitz, Sroufe, Stewart, & Leffert, 1990; should almost always be employed with other psychological and Whalen, Henker, Hinshaw, & Granger, 1989). Jacobvitz et al.
educational interventions, well-established empirical data have noted that reduced levels of prosocial behaviors may be associated consistently demonstrated the potential benefits of the stimulants with relatively high doses of stimulant medication. However, some on symptoms associated with ADHD, including inattention, over- studies examining the effects of stimulant medication on children’s activity, and impulsivity (for reviews, see Bennett et al., 1999; social behaviors have been more encouraging (see Hinshaw, Brown & Sawyer, 1998; Phelps et al., 2001). The findings have 1991). In one controlled trial, children who were receiving placebo been corroborated on laboratory performance tasks, direct obser- doses versus stimulants were more negatively engaged, used more vations of behavior in structured classroom settings, and on be- aversive leadership techniques, and were also rated as less likable havioral rating scales completed by caregivers and teachers.
by their peers (Buhrmester, Whalen, Henker, McDonald, & Hin- Methylphenidate (Ritalin and others), a commonly used stimulant shaw, 1992). Clearly, much more research is needed in this area to medication, has been demonstrated to exert significant positive clarify some of the consistencies with regard to social behaviors, effects on measures of attention and academic efficiency for chil- and until further data are forthcoming, careful monitoring must be dren with ADHD in the classroom setting (DuPaul & Rapport, 1993). There is also a corpus of research to indicate that for Regarding the long-term effects of stimulant medication, the children without ADHD, stimulant medication may enhance majority of studies have focused on height and weight suppression, mother– child relationships by reducing frequency of commands cardiovascular effects, and drug dependence and abuse. As a (Barkley & Cunningham, 1979; Barkley, Karlson, Strezelecki, & function of stimulant therapies, however, growth suppression ap- Murphy, 1984). Psychostimulants have also been effectively used pears to be both dose dependent and transient (Klein & Mannuzza to reduce aggression in some ADHD children (for a review, see 1988). Nonetheless, because stimulants are frequently prescribed well into adolescence and even adulthood, ongoing monitoring of SPECIAL SECTION: PEDIATRIC PSYCHOPHARMACOLOGY height and weight is imperative (Bennett et al., 1999). There has groups demonstrated marked reductions in symptoms over time, also been concern regarding the effects of stimulant medication on stimulant medication was more effective than behavioral treat- cardiovascular functioning, due to the fact that stimulants increase ments for the management of symptoms associated with ADHD.
heart rate, blood pressure, and respiration in the short-term. How- For children who had comorbidity of symptoms including aggres- ever, these effects have been found to be clinically insignificant sion, oppositional behavior, and even internalizing symptoms, and transient (Zeiner, 1995). Recently, there has been much con- however, combined treatments of both medication and behavior cern about patients potentially abusing stimulant medication, par- therapy proved superior to behavioral treatment used alone or to ticularly during adolescence, when many youths are at marked risk traditional treatments provided in the community. This finding is for drug abuse. Concerns regarding abuse are apt to be highest important for several reasons. Children with ADHD commonly when there is comorbidity of other disruptive behavior disorders present with comorbid diagnoses. Also, in the MTA study, parents (e.g., conduct disorder). Fortunately, the few available studies preferred the behavioral therapy condition to the medication-alone suggest that when children and adolescents are managed on ap- treatment (MTA Cooperative Group, 1999).
propriate doses of medication, they are at no greater risk forabusing stimulants than are peers who are not managed with stimulants (American Academy of Pediatrics, 2001).
The most commonly employed stimulants include methylpheni- The antidepressants traditionally have been used for those target date, both in immediate and sustained-release preparations symptoms associated with major depressive disorder, including (Ritalin, Ritalin-SR, Concerta), dextroamphetamine (Dexadrine) depressed mood, appetite change (i.e., increase or decrease in and amphetamine– dextroamphetamine mixtures (Adderall), and, weight), anhedonia, anergia (lack of energy), decreased concen- less commonly, pemoline (Cylert). Because of a small number of tration, changes in psychomotor activity or sleep patterns, and reports in the United States of acute liver failure, the Food and recurrent thoughts of death. The clinical use of antidepressants, Drug Administration (FDA) has recommended that pemoline not like that of stimulants, continues to grow explosively in pediatric be ordinarily considered a first-line drug therapy for children and adolescent populations, although proof of the efficacy of diagnosed with ADHD (Abbott Pharmaceuticals, 1996).
antidepressants in these age groups remains inconclusive at best Recently, clinical use of Adderall has gained widespread appeal (for reviews, see Brown & Sawyer, 1998; Emslie, Walkup, in the management of children with ADHD. Only three studies can Pliszka, & Ernst, 1999; Phelps et al., 2001). The antidepressants be located that have compared Adderall with standard doses of may be divided into several classes, including the tricyclics, the Ritalin (Pelham et al., 1999, 2000; Swanson et al., 1999). Findings selective serotonin reuptake inhibitors (SSRIs), monoamine oxi- revealed that both stimulants were superior to placebo in improv- dase inhibitors, and the atypical antidepressants.
ing academic productivity as well as ratings of behavior. Adderall Studies of tricyclics have not revealed efficacy greater than that was found to be superior to Ritalin in cases in which the effects of for placebo (Birmaher, 1998; Boulos et al., 1991; Kutcher et al., Ritalin dissipated at midday and in the late afternoon. There was a 1994; Kye et al., 1996). The lack of clearly defined efficacy and low side-effect profile for both stimulants. Thus, Adderall appears the adverse side-effect profile of the tricyclic antidepressants (in- to be at least as effective as Ritalin in the short-term in improving cluding reports of sudden cardiac death; Riddle, Geller, & Ryan, behavior and academic productivity for children identified with 1993; Varley & McClelland, 1997; Werry, 1995) suggest that ADHD. For this reason, Pelham et al. (2000) recommended the use these agents should not be routinely employed in the management of Adderall, particularly for children in whom the effects of Ritalin of depression in children and adolescents.
Since their introduction nearly 15 years ago, the SSRIs have A final issue regarding the stimulants relates to the relative been widely prescribed for adults due to their documented safety efficacy of stimulant medication and behavioral therapy or their and favorable side-effect profile. SSRI antidepressants currently combined effects in managing the symptoms associated with available in the United States are fluoxetine (Prozac), sertraline ADHD. Of further interest is whether the combination of stimulant (Zoloft), paroxetine (Paxil), and citalopram (Celexa). Of these, drug therapy and behavior therapy is more potent than either only sertraline has received FDA approval for use in pediatric treatment used alone. This issue has been the topic of the largest populations. Fluvoxamine (Luvox), though a potent inhibitor of clinical trial sponsored by the National Institute of Mental Health serotonin reuptake, is approved only for the treatment of and is one of the more definitive long-term studies addressing the obsessive– compulsive disorder in both adults and children. Al- issue of multimodal therapies in pediatric populations. The Mul- though preliminary and still emerging, the literature has been timodal Treatment Study for Children With ADHD (MTA Coop- generally favorable regarding the efficacy of the SSRIs in the erative Group, 1999) examined the relative efficacy of 14 months management of pediatric depression (Alderman, Wolkow, Chung, of four treatments for managing ADHD in 570 children (7–9 years & Johnston, 1998; Ambrossini et al., 1999; Apter et al., 1994; old) with ADHD who were randomly assigned to one of four Cosgrove, 1994; DeVane & Sallee, 1996; Emslie & Mayes, 2001; treatment groups. Treatments included (a) behavioral therapy Emslie, Rush, Weinberg, & Kowatch, 1997; Martin et al., 2000; alone (i.e., 35 sessions of behavioral parent training, 10 teacher– Rey-Sanchez & Gutierrez-Casares, 1997; Sallee, Hilial, Dough- school consultations per school year, a classroom aide, and an erty, Beach, & Nesbitt, 1998; Wilens, Spencer, Biederman, & intensive summer treatment program); (b) medication management Schleifer, 1997). Despite generally positive recommendations, alone (i.e., stimulant medication administered 7 days/week); (c) most authors are careful to point out that not enough carefully combined behavioral training and medication management; and controlled randomized trials exist to make definitive recommen- (d) a community control group of children who received traditional dations. Thus, although the strength of the evidence is as yet therapies for ADHD. Findings revealed that although all four undetermined, at least some data suggest that the SSRIs may be superior to placebo in managing select target symptoms. Adverse agent be used to reduce psychotic symptoms only as a last resort, effects, including nausea, overactivity, insomnia, weight loss, and when children have failed to respond to other antipsychotic agents.
(rarely) dermatitis, are of significant concern, though these have It is important to note that the overuse of antipsychotics and generally been reported to be minor and transient. Because of the mood stabilizers in pediatrics is an area of considerable contro- promising data in early controlled trials of SSRIs and some spec- versy. A recent study of institutionalized children found that an- ulation that prompt treatment with antidepressants may provide tipsychotics were the most frequently used category of medication long-term protective effects (Martin et al., 2000), further well- (35% of all admissions to the facility were studied; Connor, designed, placebo-controlled, double-blind studies are clearly war- Ozbayrak, Harrison, & Melloni, 1998), and a high rate of prescrip- ranted, particularly over the long-term with pediatric populations.
tions of mood stabilizers was found as well. Connor and colleagues One atypical antidepressant, buproprion (Wellbutrin, Wellbutrin noted that antipsychotics were generally used in the absence of a SR, also marketed as Zyban for smoking cessation) has demon- diagnosis of psychosis, a tic disorder, or bipolar disorder. In a strated some promise in double-blind clinical trials with children report on psychoactive drug prescription in pediatric outpatients, diagnosed with ADHD (Barrickman et al., 1995). In particular, Kaplan, Simms, and Busner (1994) also noted that 65– 67% of when children have been refractory to stimulant medication, when children surveyed were prescribed antipsychotics without a corre- there has been a remarkable personal family history of tics, or sponding diagnosis of a psychotic disorder.
when there is a family member at risk for abusing or selling One antipsychotic medication that has gained popularity in the stimulant medication, the use of buproprion may be a reasonable clinical management of psychotic symptoms is risperidone alternative to the stimulants. Studies suggest that buproprion may (Risperdal). Open trials have been encouraging and suggest that reduce symptoms of ADHD (Barrickman et al., 1995), although its risperidone significantly reduces target symptoms of psychotic adverse effects are numerous and include insomnia, agitation, behaviors (Armenteros, Whitaker, Welikson, Stedge, & Gorman, confusion, irritability, and possible hypertension. Bupropion use is 1997; Zuddas, Pintor, & Cianchetti, 1996), aggression (Horrigan & contraindicated in patients with histories of eating disorder or Barnhill, 1998), and behaviors associated with pervasive develop- mental disorder (Perry, Petaki, Munoz-Silva, Armenteros, & Silva,1997; Purdon, Lit, Labelle, & Jones, 1994); few extrapyramidalsymptoms have been reported in the adult literature. However, many more controlled trials are needed before the efficacy andsafety of risperdal with pediatric populations can be established.
There is a paucity of data regarding the use of antipsychotic Similarly, the newer atypical agents ziprasidone (Geodon) and medications with childhood schizophrenia. Haloperidol (Haldol) quetiapine (Seroquel) have become increasingly used, largely due has been the mainstay in the management of childhood-onset to their improved side-effects profiles. But as with any other schizophrenia, and the efficacy of haloperidol has been established atypical antipsychotic, there are no definitive studies regarding in a number of controlled clinical trials (for a review, see Ernst et their use in children, so their use cannot be recommended in most al., 1999). The related drug, pimozide (Orap), was used in the treatment of severe Tourette’s disorder, but this use is no longer In summary, the antipsychotics have been the treatment of generally recommended due to the potential for cardiotoxicity.
choice in the management of psychotic symptoms in pediatric Haloperidol has the advantage of being relatively less sedating populations. Those agents that have received at least a glimmer of than traditional antipsychotics (for a review, see Campbell & empirical support include clozapine, haloperidol, loxapine, and Armenteros, 1996), although the incidence of extrapyramidal risperidone. As noted above, however, clinical use of these agents symptoms (e.g., involuntary movements, tremors, muscle spasms, has far exceeded the available literature regarding efficacy and balance difficulties) is relatively high.
safety. Many more controlled trials are needed before their effi- The atypical antipsychotics represent a potential advance in the cacy and safety with pediatric populations can be confirmed.
treatment of child psychosis. Olanzapine (Zyprexa) was approvedfor use by the FDA in 1996 and is considered an atypical neuro- Mood Stabilizers and Anticonvulsants leptic with the advantage of having fewer extrapyramidal adverseeffects than haloperidol (Stahl, 1999). Adverse effects include Lithium carbonate is frequently prescribed in the management sedation, weight gain (which can often be significant), elevated of bipolar disorders in adults. Although there are few studies serum prolactin levels, and anticholinergic effects (e.g., dry eyes, documenting bipolar disorders in pediatric populations, lithium mouth, throat, constipation). However, as with many psychotropic therapy has received widespread clinical use. There are in fact agents for pediatric populations, many more studies are needed several controlled trials suggesting that lithium can be effective in with olanzapine prior to endorsing its efficacy and safety for the management of symptoms associated with bipolar disorder in children. There have been several open and double-blind clinical adolescents (Geller et al., 1998). Campbell and colleagues (Camp- trials establishing the efficacy of the atypical antipsychotic cloza- bell et al., 1995; Campbell, Small, & Green, 1984) and Rifkin et al.
pine for childhood psychotic disorders that have been refractory to (1997) have demonstrated the efficacy of lithium in treating ag- traditional antipsychotic agents (Fleischaker, Schulz, & Rem- gressive behavior and conduct disorder; according to their find- schmidt, 1998; Kumra et al., 1998; Turetz et al., 1997). Clozapine ings, some children showed marked improvement. No studies has proved superior to haloperidol in reducing psychotic symp- could be located that have examined the efficacy of lithium ther- toms (Kumra et al., 1996). Nonetheless, because of the potential of apy for young children. Clearly, additional research is needed severe, possibly fatal, adverse effects associated with clozapine regarding the safety and efficacy of lithium for pediatric (agranulocytosis and cardiotoxicity), it is recommended that this SPECIAL SECTION: PEDIATRIC PSYCHOPHARMACOLOGY Anticonvulsant or antiepileptic medications have been used Clomipramine (Anafranil) has been used in the management of successfully for many years in the management of seizure disor- obsessive– compulsive disorder. Double-blind controlled trials ders in children and adolescents. There has been an emerging with pediatric populations have documented significant decreases clinical literature to suggest that anticonvulsant agents may also in obsessive– compulsive symptomatology when comparing clo- reduce behavioral problems in children who do not have seizure mipramine to placebos or desipramine (DeVeaugh-Geiss et al., disorders (for a review, see Phelps et al., 2001). Anticonvulsant 1992; Leonard et al., 1991). Because clomipramine has a structure agents include phenobarbital, phenytoin (Dilantin), carbamazepine that is essentially identical to tricyclic antidepressants, ongoing (Tegretol), and valproate (Depakote, Depakene) (Brown & Saw- evaluation of side effects, such as weight gain, anticholinergic side effects, and cardiotoxicity are imperative (Riddle et al., 1993).
Some investigators have examined valproate (Delitio, Levitan, Serum drug levels are also required, adding to the cost and incon- Damore, Hajal, & Zambenedetti, 1997; Papatheodorou & Kutcher, venience of this agent. The use of clomipramine in children, as in 1993; Papatheodorou, Kutcher, Katic, & Szalai, 1995; West, Keck, adults, has largely been supplanted by the SSRIs.
& McElroy, 1995) and carbamazepine (Tegretol) for the purpose Clonazepam (Klonopin) has been found to be effective in the of reducing manic symptoms in adolescents. Of concern is the management of separation anxiety and generalized anxiety disor- report in one investigation of children receiving carbamazepine for der in children (Graae, Milner, Rizzotto, & Klein, 1994) as well as aggression. Nearly one third of the participants in the sample panic disorder in adolescents (Kutcher, Reiter, Gardner, & Klein, developed behavioral toxicities that included mania, impulsivity, 1992). Adverse effects are dose dependent and include sedation, and sedation (Pleak, Birmaher, Gavrilescu, Abichandani, & Wil- dizziness, and ataxia. As with any benzodiazepine, there is the risk liams, 1988). Valproic acid has been successfully used for both of long-term physiological dependence, and abrupt cessation of children and adults with developmental disabilities, including medication can be potentially dangerous. There is also a concern mental retardation and cyclic mood disorders (Poindexter et al., that treatment with anxiolytics may render exposure-based treat- 1998). Target symptoms of irritability and behavioral cycling ment interventions ineffective and may thus interfere with behav- appear to be particularly responsive to valproic acid, although ioral therapy. These factors are significant and constrain the use of self-injurious behavior and aggression have also been found to clonazepam, other benzodiazepines, and similar sedatives in diminish in open clinical trials (Kastner, Finesmith, & Walsh, 1993). The newer anticonvulsants, including gabapentin (Neuron- It is recommended that the treatment of pediatric anxiety disor- tin), tiagabine (Gabitril), and lamotrigine (Lamictal), have been ders always include psychological interventions (e.g., behavioral, preliminarily studied in the management of cycling mood disor- cognitive– behavioral) as a first-line treatment approach and that ders in children and adolescents, although much more investiga- medication be considered only when psychological therapies have tion is needed regarding their safety and efficacy prior to endorsing failed. Clearly, additional clinical trials are necessary to establish the safety and efficacy of anxiolytics both in the long- and the To date, the FDA approves routine use of anticonvulsants only for the management of seizure disorders and manic phases duringbipolar disorder (Vining, Carpenter, & Aman, 1999). Nonetheless, Miscellaneous Psychotropic Medications clinical use of these medications for a number of psychiatricdisorders, including behavioral disorders, has increased markedly Clonidine (Catapres) is a centrally acting antihypertensive drug (Vining et al., 1999). Concern remains regarding the overuse of that has been observed to reduce symptoms associated with anticonvulsant agents for disorders and for populations for which ADHD, particularly overactivity, impulsivity, and inattention research has not established efficacy and safety. In short, clinical (Hunt, Capper, & O’Connell, 1990). Clonidine has been less useful use appears to have exceeded available research data. In addition, for managing symptoms associated with attention and concentra- the behavioral and cognitive toxicities associated with these med- tion. Guanfacine (Tenex) is a longer acting medication and has ications mandate that children’s behavior, learning, and mood effects similar to those of clonidine, with fewer adverse effects.
receive ongoing monitoring by means of behavioral observation There had been significant increases of these medications in the across all settings and psychometric evaluation on at least a yearly management of ADHD and other disruptive behavior disorders in basis (American Academy of Pediatrics, 1985).
the early to mid-1990s. Unfortunately clinical use of these psycho-tropic medications has far surpassed research demonstrating their efficacy and safety. Adverse effects of these medications includehypotension, depressive symptoms, and sedation (Werry & Aman, There are substantial empirical data supporting the efficacy of 1999). The use of clonidine should be governed by serious con- behavioral, cognitive– behavioral, and psychosocial interventions cerns regarding its high degree of toxicity in overdose. The nico- for the treatment of childhood anxiety disorders (Morris & tine receptor antagonist mecamylamine (Inversine) has a long Kratochwill, 1998; Ollendick & King, 1998), although far fewer history of use in adults in the treatment of hypertension. It has studies are available regarding psychotropic medications for man- recently been investigated in the treatment of childhood Gilles de aging these disorders in children (Allen, Leonard, & Swedo, 1995; la Tourette disorder (Silver et al., 2001; Young, Shytle, Sanberg, & Kearney & Silverman, 1998). Unfortunately, as in other classes of George, 2001). A recent randomized controlled trial did not find it psychotropics, there is increased use of anxiolytic medications and to be more effective than placebo in managing Tourette’s disorder sedatives for pediatric populations due to the movement toward in children (Silver et al., 2001). This, along with the fact that it is short-term management of psychiatric disorders and cost contain- potentially quite toxic, does not support its use in children at the ment (Allen et al., 1995; Kearney & Silverman, 1998).
Although the use of herbal remedies has recently been consid- Sawyer (1998) for a complete review. Brain imaging and other ered in the adult literature, far fewer studies are available in the specialized assessments (PET and EEG) have been widely used in pediatric literature. A complete description of available herbal research programs of medications in various psychiatric popula- remedies is not possible within the scope of this review, although tions, but their routine use in monitoring drug response is infea- we do review St. John’s wort, an herbal remedy that has recently sible, due to their low yield and high cost.
been investigated with adults and has potential efficacy in the management of mild depression and dysthymia (Werry & Aman, fied as unstructured interviews, semistructured interviews, struc- 1999). Its use in children is not recommended until further data tured interviews, and symptom checklists. Limitations of struc- regarding its safety and efficacy for the pediatric population are tured interviews include their length and difficulties with their forthcoming (Werry & Aman, 1999), particularly in light of recent sensitivity and specificity to individual symptoms of various dis- reports of significant interactions with other prescribed drugs and orders. The semistructured interview does provide some compro- a randomized controlled trial in adults that did not find it of use in mise, although significant training is required on the part of the the treatment of major depression (R. C. Shelton et al., 2001).
interviewer. Finally, the use of symptom checklists provides prac- Because patients may not readily reveal use of St. John’s wort or titioners with prompts to assure that all of the major areas of the similar compounds (Walter & Rey, 1999), clinicians should ask diagnosis are included. Thus far, structured interviews seem to be specifically about the use of herbals, and their use should be the most sensitive to psychotropic drug effects (for a review, see strongly discouraged if the patient is taking prescribed psycho- tropics or other agents that have known interactions with herbal their cost-effectiveness, abundance of normative data that allowfor comparison across children, and the fact that relevant behaviors Monitoring and Assessing Psychotropic Drug Effects may be sampled across different settings and domains over time.
Most important, rating scales that are well constructed are partic- There are a number of instruments and procedures for the ularly sensitive to psychotropic drug effects in children (for re- assessment and monitoring of psychotropic drug effects in the views, see Aman & Pearson, 1999; Brown & Sawyer, 1998). The domains of learning, psychosocial functioning, and physical func- reader is encouraged to review Aman and Pearson (1999), partic- tioning. For the medication effects to be fully appreciated, it is ularly for those rating scales that have demonstrated psychotropic necessary that monitoring be based on systematic data from a variety of sources (e.g., school, home) rather than simply on the clinician’s global impression (Aman & Pearson, 1999).
ically used in practice settings to identify high-frequency and Prior to prescribing, the clinician should ob- global behaviors. Their advantages include the ability to provide tain a baseline medical history and conduct a physical exam to rule the practitioner with a valid display of children’s behavior in an out organic causes of mental distress or other central nervous ecologically valid setting (e.g., classroom, playroom), their ability system pathology (Zametkin & Yamada, 1999). History should to allow comparisons between behaviors in test situations and include information regarding immunizations, previous hospital- those in more naturalistic settings, their ability to be continuously izations, trauma, transfusions, allergies, current medication, previ- repeated without practice effects, and their use with children who ous substance abuse history, family medical and mental health have serious psychopathology or who may be generally uncoop- erative in a structured assessment setting. Limitations of direct Because psychotropic medications affect many organ systems, a observations include their labor intensiveness, expense, and careful review of systems is also necessary. As Zametkin and changes in ratings that may be a function of observer fatigue rather Yamada (1999) have observed, some psychological symptoms than the children’s behavior. Direct observations are particularly may mimic adverse effects of psychotropic medications, and for sensitive to psychotropic medications and to various doses of this reason, establishing a baseline of such symptoms is important.
medications (DuPaul & Kyle, 1995). Several observational codes A thorough physical and neurological examination is also impor- are available for clinical use with children diagnosed with various tant to rule out medical masquerades and to provide a baseline.
psychiatric and developmental disorders, and the interested reader Because many psychotropic agents have the potential of altering is referred to Aman and Pearson (1999) and Brown and Sawyer speech and language skills, assessing speech production, rate, (1998) for a review of the various direct observational schedules.
volume, and coherence is prudent (Zametkin & Yamada, 1999).
Objective monitoring of medication effects and careful use of batteries are available to the practitioner for use in assessing caregivers as informants are required, as children are frequently children’s responses to psychotropic medication. These include unreliable reporters of physical symptoms or medication side performance tests, computerized assessments, and intelligence and effects. Unfortunately, there is little objective monitoring of psy- achievement measures. T. Shelton and Barkley (1995) have cau- chotropic drug effects in the practice setting (Brown & Sawyer, tioned that performance on various cognitive measures may be 1998), although several rating scales, checklists, laboratory stud- confounded by other abilities, including attention, memory, lan- ies, and physical examinations are available. Rating scales are guage, and intellectual functioning. Computerized assessments particularly useful in assessing those adverse effects of pharma- allow for objectivity and standardization, precision, novelty of the cotherapy that may not necessarily be spontaneously reported by tasks, and immediate scoring, although disadvantages include high caregivers. Although a review of rating scales is not possible cost, questionable ecological validity to natural settings, and psy- within the scope of the present review, the reader is encouraged to chometrics that remain to be demonstrated. Finally, intelligence examine the work of Zametkin and Yamada (1999) and Brown and and achievement tests are often used in the assessment of medi- SPECIAL SECTION: PEDIATRIC PSYCHOPHARMACOLOGY cation effects, although their sensitivity to medication effects is as well as the concern that drug therapy may replace important fairly low because they assess stable constructs and global indices psychotherapy or special education programming because it is that are rarely affected by psychotropic medication (Brown & more cost effective in the short-term but not necessarily more effective in the long-term (Brown & Sawyer, 1998). Informed Investigators have diligently searched for either a specific in- consent, the right to refuse treatment, issues of custody, confiden- strument or package of measures that may predict response to tiality, and the patient’s best interest remain essential standards of psychotropic medication. As opposed to the many instruments practice with pharmacotherapy as with any traditional assessment available to monitor psychotropic response and adverse effects, and psychotherapy conducted by practicing psychologists. It also there does not appear to be a specific instrument available to is important that children give assent for medication as a means of predict response to any class of medication. The importance of fostering a therapeutic alliance and encouraging some autonomy systematically using multiple objective assessments across settings and responsibility with the medication regimen (Brown & Sawyer, rather than the sole reliance on clinical impressions in the office 1998; Krener & Mancina, 1994; Shouten & Duckworth, 1999).
Krener and Mancina have observed that including the child oradolescent in the consent process can help to avoid feelings of Treatment Acceptability and Satisfaction coercion on the part of the child and may serve to enhance thetherapeutic goals of treatment and the developmental interests of It should be of interest to practicing psychologists that in the the children. Careful attention to risk management must be the community, psychotropic medication is generally rated less favor- standard and should include systematic documentation, consulta- ably than the individual psychotherapies or behavioral approaches tion with colleagues, and making realistic promises to children and (Corkum, Rimer, & Schachar, 1999; Pelham, 1999; Power, Hess, their families regarding medication efficacy and safety (Shouten & & Bennett, 1995). It should be noted, however, that caregivers are apt to be more willing to medicate their children when theyparticipate in a systematic drug trial where ongoing efficacy is documented as well as any adverse side effects (Johnston & Fine,1993). Further, those intervention approaches that involve a com- Polypharmacy, escalating use of all psychotropics, particularly bination of pharmacotherapy and psychotherapy have consistently stimulants and serotonergic antidepressants, and the off-label use been demonstrated to be more acceptable to caregivers and teach- of anticonvulsant medications for mental health purposes are in- ers than medication used alone (Liu, Robin, Brenner, & Eastman, creasingly common prescribing patterns in modern child practice 1991; Pelham, 1999; Power et al., 1995). Teachers’ attitudes have (Jensen et al., 1999; Zito et al., 2000). A reasonable amount of been demonstrated to be similar to caregivers’ attitudes (Power et support exists for the use of stimulant medications, at least in the al., 1995) and may be modified by providing teachers with feed- treatment of certain facets of ADHD. However, well-designed, back regarding potential for response to medication and ongoing controlled-outcome studies of anticonvulsant medications, seroto- treatment efficacy. Children’s attitudes regarding stimulant medi- nergic antidepressants, and atypical antipsychotics are scarce to the cation vary according to developmental level and the nature of the point of nonexistence. Although these agents are of benefit to a problem and may vary across the course of treatment (for a review, number of children for whom they are prescribed, relatively little see Phelps et al., 2001). It is imperative that clinicians evaluate attention has been paid to the development of rational strategies carefully the attitudes of all significant individuals who are apt to designed to optimize their use. A particular deficit in this regard is be involved in the psychopharmacology treatment program, be- the general lack of studies that address the important issue of cause caregiver, teacher, and child attitudes are apt to influence combined treatment outcome (Weisz & Jensen, 1999).
adherence to medication protocols (Phelps et al., 2001). Finally, it Practicing psychologists who provide clinical services to chil- has been demonstrated that provider attitudes significantly affect dren and adolescents will have increasing opportunities to work clinical care (Brown, 2002), and attention to practicing psycholo- with youth who are being managed on psychotropic medication.
gists’ attitudes about pharmacotherapy are likely to determine This will likely include increased consultation activities with pe- whether children are managed with pharmacotherapy for behav- diatricians or family practitioners regarding decisions to use med- ication and predict response for particular clients. These activities Even when psychotropic medication is thought to be particularly will increase concomitantly the demands for training opportunities beneficial, children and caregivers may fail to adhere to prescribed at the predoctoral, postdoctoral, and continuing education levels. It regimens. The stages-of-change model advanced by Prochaska, is to be hoped that professional psychologists’ greater involvement DiClemente, and Norcross (1992) provides a useful framework for as applied researchers and as clinicians who directly provide understanding the failure of families to initiate treatment and psychotropic medications will result in greater empirical validation adhere to it. Thus, whether or not the clinician prescribes medica- of the practice of pediatric psychopharmacology.
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