Antipsychotic Medication in Children and Adolescents: A Pediatrician's Perspective Betsy Busch, MD Why should pediatricians and other primary caregivers become knowledgeable about antipsychotic medications? For many community pediatricians, the knowledge base needed to prescribe antipsychotic medications surpasses their residency training in psychopharmacology. Yet, there is a nationwide shortage of child and adolescent psychiatrists, and they are particularly scarce in some rural and poor urban neighborhoods. Even when child and adolescent psychiatrists are nearby, it may be several months before an appointment can be scheduled for a new patient. Other common obstacles include inadequate availability of public or other transportation to help patients reach the psychiatrist's office, lack of health insurance, or insurance restrictions that would result in prohibitive out-of-pocket expenses for a family. These unfortunate but common obstacles lead to insufficient access to psychiatric consultants for some primary caregivers and their patients. As a result, community pediatricians must become proficient and knowledgeable prescribers of antipsychotic medications. Even when a child and adolescent psychiatrist initiates treatment with an antipsychotic drug for a child or adolescent in your practice, the primary care physician's office and nearby clinical laboratory may continue to be the most convenient location for both the necessary pretreatment (baseline) medical assessments and the subsequent medical monitoring of the patient described in Dr. McClellan's excellent review article. The primary caregiver may also have greater experience than some child psychiatrists with the assessment and management of the wide range of metabolic, endocrine, cardiac, and other side effects that can result from the use of second-generation antipsychotic medications. It is important, therefore, for the primary caregiver to have adequate knowledge of the complex medical risks, benefits, and individual properties of antipsychotic medications for the overall health of their patients taking these medications. Dr. McClellan provides a current overview of what is known about the efficacy and safety of these medications in pediatric patients, and summarizes the clinical studies of antipsychotics in children and adolescents, given for a variety of Food and Drug Administration-approved and "off-label" indications. Dr. McClellan also indicates that we still have much to learn about the use of these medications in children. Interdisciplinary Collaboration A diagnostic consultation with a child and adolescent psychiatrist before initiating treatment with an antipsychotic drug is usually the preferred option. But if no initial psychiatric consultation is available before treatment must be started, a subsequent consultation for your patient (if possible) still can be very helpful. The consultant can review your (provisional) diagnostic formulation and ascertain that no comorbid conditions or complicating factors have been overlooked. The consultant also can review the patient's current pharmacologic and nonpharmacologic management, and offer suggestions that might further contribute to a positive outcome for the patient. As pediatric patients get older and enter subsequent developmental phases, the gap may increase between their levels of competence and the age-appropriate academic and cognitive demands and the expectation of greater interpersonal competence (eg, with friends, families, teachers, coaches) that he or she will encounter. This process often generates new, more complex variations of prior interpersonal, academic, and other problems and can worsen patients' functional impairment, diminish their self-esteem, and create in patients a more pessimistic outlook for their future. Episodic reassessments by the psychiatric consultant, if possible, offer the primary caregiver a longitudinal, yet fresh, look at the patient's diagnostic picture, including any newly emergent comorbid conditions. The psychiatric consultant may suggest medication or dosage changes and suggest other medical or nonmedical interventions that may now be appropriate. I certainly find it helpful to pick up the phone and discuss a patient taking antipsychotic medication with a consulting psychiatrist when new dilemmas or difficult situations arise. Nonmedical Interventions I strongly agree with Dr. McClellan that antipsychotic medication should be viewed as only one contribution to a much more extensive system of nonmedical, longitudinal services (eg, psychotherapeutic, educational) to a child and his or her family. If a child is impaired enough to require treatment with an atypical antipsychotic medication, it is almost certain that the child will present significant child-rearing, family, educational, social, and other challenges. Parents of these children usually should receive psychotherapeutic support, instruction in proper behavior management techniques, and guidance about effective child-rearing behaviors. These services usually are needed over many years, as new parenting challenges arise over time. Such a therapeutic relationship can enhance parenting effectiveness and improve parent-child interactions at home. Children and adolescents with severe neurobehavioral disorders also require effective, longitudinal psychotherapy; the child's therapist can help the young patient to learn more adaptive responses to problem situations and to establish and work toward specific behavioral and psychological goals. When a specific problem needs focused attention, the addition of short-term cognitive-behavioral therapy (CBT) can be helpful. This treatment modality may prove helpful to children with varied concerns (eg, overcoming specific phobias, decreasing compulsions, managing angry feelings to reduce behavioral outbursts, improving self-concept and reducing self-deprecation, or improving sleep hygiene/scheduling). CBT, unlike other psychotherapies, is usually highly prescriptive, has "homework" each week (ie, the patient is expected to keep a diary of problematic situations or practice a specific behavioral exercise), tends to work on 1 specific problem over 8-12 weeks, and then is discontinued. It can be initiated alone or can be used now and then for brief, targeted, adjunctive help, in addition to other patient or family psychotherapies. Finding cognitive-behavioral therapists can be difficult; the Resources section has some suggestions. Finally, the child's therapist or therapists also should be encouraged to participate in special educational planning (at IEP [individualized education program] meetings), to describe the conditions and approaches that will support both the patient and the teachers sufficiently for learning to occur. Practical Considerations Communication At the start of a collaboration with consulting mental health (and any other) professionals, it is helpful to discuss and agree upon how and how often you will share information with one another about the patient's response to treatment, side effects, and clinical course. Sharing information among caregivers and consultants is the only way to be certain that your patient is receiving well- coordinated care and a unified therapeutic effort. Treatment Planning Several preparatory tasks should precede the initiation of a clinical trial of antipsychotic medication. First, parents and, as age-appropriate, patients should be informed about the extensive range of potential side effects and possible benefits associated with second-generation antipsychotic medications. Second, patients and their families need to understand how often they will need to return for follow-up visits to monitor weight gain and calculate body mass index; to reassess extrapyramidal side effects and tardive dyskinesia; and to undergo blood tests to monitor the patient's metabolic, endocrine, and cardiovascular health, as described in Dr. McClellan's review. Third, baseline data on these same measures should be obtained. If a second-generation antipsychotic medication is being prescribed in a nonemergency situation, consider suggesting to patients and their families that they begin a structured weight control dietary program and institute a daily exercise routine before starting the medication because of the difficulty in managing the anticipated weight gain and its serious consequences. In emergency situations, discuss with the patient and family your plan to ask them to implement these essential programs as soon as the patient has stabilized. Polypharmacy In theory, I agree with Dr. McClellan's recommendation that "as a general rule, the use of multiple psychotropic agents is probably best avoided." This principle, however, can be difficult to follow. Severe childhood psychiatric and neurobehavioral disorders may evolve over childhood, with less severe symptoms initially and "layers" of new symptoms or behaviors emerging over time. If psychopharmacologic intervention seems indicated, most pediatricians will try at first to use a medication with relatively low levels of risk. By the time the physician thinks that an antipsychotic medication may be necessary, it may be difficult to determine whether it will be safe to taper and discontinue all other medications before starting the neuroleptic, especially if the parents and physician are trying to avoid a psychiatric hospitalization. Severe psychiatric or behavioral disturbances often have one or more comorbid psychiatric conditions; multiple comorbid conditions often require several psychoactive medications to optimize outcomes.[2-4] If the patient will be taking more than one medication, it is important to avoid adverse drug-drug interactions (see the Resources section). When titrating antipsychotic medication, the psychiatrists I know use the aphorism "Start Low, Go Slow." This means that antipsychotic medications are best initiated at a low dose, and increased gradually, in nonhospitalized pediatric patients. It also is prudent to taper antipsychotic medication gradually in order to diminish the risk for withdrawal dyskinesias. For pediatric outpatients starting an antipsychotic medication, the physician's challenge is to titrate slowly enough to be certain that a low dose is truly inadequate before increasing the dose further (and risking more side effects), while at the same time trying to relieve the patient's distress as compassionately and quickly as possible. Resources In this section, I list a few articles, Websites, and other resources that I have found personally helpful as reference materials relating to severe psychiatric and behavioral disturbances and atypical antipsychotic. There are many other excellent resources with similar information; this is just a sampling. Whatever resources you choose to use, they must be updated regularly. Review Articles A handful of review articles on the use of antipsychotic agents and the diagnosis and management of the conditions for which they are used can be very helpful. In addition to Dr. McClellan's article, other recently published articles that I have found helpful include the following: Baroni A, Lunsford JR, Luckenbaugh DA, et al. Practitioner review: the assessment of bipolar disorder in children and adolescents. J Child Psychol Psychiatry 2009;50:203-215. This is a detailed explanation of the continuing controversy over the diagnosis of bipolar disorder in children. The authors explain the difference between "true" pediatric bipolar disorder and what they have named "severe mood dysregulation," how to distinguish this proposed syndrome from both attention-deficit/hyperactivity disorder and childhood mania, and suggestions for assessing aggression and possible suicidal thoughts in such patients. The authors end by discussing the relative advantages and disadvantages of several pediatric rating scales for the clinical assessment of children when bipolar disorder is in the differential diagnosis. Kowatch RA, DelBello MP. Pediatric bipolar disorder: emerging diagnostic and treatment approaches. Child Adolesc Psychiatric Clin N Am 2006;15:73-108. This article provides a different version of the diagnostic debate over pediatric bipolar disorder, which concludes that "bipolar disorder not otherwise specified" is the most appropriate diagnostic category. It discusses specific interviewing questions that can differentiate patients who have bipolar disorder from those who do not, and includes a copy of a mood disorders screening questionnaire (with scoring instructions), as well as the entire K-SADS (Kiddie Schedule for Affective Disorders and Schizophrenia) mania rating section, a lengthy diagnostic instrument frequently used in studies of juvenile bipolar disorder. The entire range of medication classes that are used to treat this disorder are reviewed as well. Filipek PA, Steinberg-Epstein R, Book TM. Intervention for autistic spectrum disorders. NeuroRx: J Am Soc Exp Neurother. 2006;3:207-216. This is an excellent review of the educational responsibilities for children with autism spectrum disorders, and the pharmacologic interventions that have been shown to be helpful. A pharmacologic treatment algorithm is presented for the many associated symptoms seen in these disorders. Behavioral interventions are mentioned only briefly, however. Correll CU. Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes. J Am Acad Child Adolesc Psychiatry. 2008;47:9-20. This article has several excellent tables that summarize antipsychotic binding profiles of all antipsychotic medications (first- and second-generation), the therapeutic and adverse effects associated with each receptor's occupancy and withdrawal, a list of the assessments that are obtained at baseline and at routine follow-up, and charts focused on abnormalities in body weight and metabolic indicators. Calarge CA, Acion L, Kuperman S, et al. Weight gain and metabolic abnormalities during extended risperidone treatment in children and adolescents. J Child Adolesc Psychopharmacol. 2009;19:101-119. This article reports on 99 children treated with risperidone and followed for an average of 2.9 years. It describes the weight, body mass index, clinical and laboratory metabolic outcomes of these children at the end of the study, and the effect of concomitant stimulant medication (which did not prevent weight gain) and baseline overweight (which greatly increased the risks for abnormal laboratory values and of at least one indicator of metabolic syndrome). Becker AL, Epperson CN. Female puberty: clinical implications for the use of prolactin- modulating psychotropics. Child Adolesc Psychiatric Clin N Am. 2006;15:207-220. This excellent article describes the complex effects of elevated prolactin levels in pubertal girls on several aspects of puberty, including menstrual dysfunction, galactorrhea, and possible decreased peak bone mineral density, which may have long-term implications for later osteopenia/osteoporosis. Drug-Drug Interactions There are many Web-based tables of varying quality and ease of use. I use: Flockhart DA. Drug interactions: cytochrome P450 drug interaction table. Indiana University School of Medicine, 2007. Available at: http://www.drug-interactions.com or http://medicine.iupui.edu/clinpharm/ddis/table.asp Rating Scales and Screening Tools Several Websites provide links to rating scales that can be downloaded at no cost, or they will direct you to another Website at which you can order those available for purchase only. The School Psychiatry Program and the Mood & Anxiety Disorders Institute (MADI) Resource Center at Massachusetts General Hospital's Department of Psychiatry jointly sponsor an excellent Website with many screening materials and rating scales for the evaluation of children with behavioral and psychiatric disorders: http://www2.massgeneral.org/schoolpsychiatry/screeningtools_table.asp Neurotransmitter.net also offers a variety of child and adult questionnaires and rating scales: http://www.neurotransmitter.net/assessment_tools.html (scroll down to "websites for assessment tools") The Lundbeck Institute in Denmark offers a variety of rating scales for a host of (mostly adult) psychiatric conditions: http://www.cnsforum.com/clinicalresources/ratingscales/ratingpsychiatry/ Among the questionnaires available for .pdf download at no cost are 2 of the 3 rating scales commonly used to monitor extrapyramidal side effects: o Simpson-Angus Scale [SAS]: http://www.cnsforum.com/clinicalresources/ratingscales/ratingpsychiatry/side_effect s/#Simpson o Abnormal Involuntary Movement Scale [AIMS]: http://www.cnsforum.com/clinicalresources/ratingscales/ratingpsychiatry/side_effect s/#AIMS Miscellaneous rating scales: o In 2005, an article introduced a new rating scale designed to characterize aggression in pediatric patients was published: Hellings JA, Nickel EJ, Weckbaugh M, et al. The Overt Aggression Scale for rating aggression in outpatient youth with autistic disorder: preliminary findings. J Neuropsychiatry Clin Neurosci. 2005;17:29-35. Available online at: http://neuro.psychiatryonline.org/cgi/content/full/17/1/29 o Finally, the Child Behavior Checklist is a widely used, well-normed, broad-behavior rating scale for youth 6-18 years old. It has been translated (and is available) in many languages. It is only available for purchase, at: http://www.aseba.org/products/cbcl6-18.html References 1. Kim WJ. Child and adolescent psychiatry workforce: a critical shortage and national challenge. Acad Psychiatry. 2003;27:277-282. 2. Gerhard T, Chavez B, Olfson M, et al. National patterns in the outpatient pharmacological management of children and adolescents with autism spectrum disorder. J Clin Psychopharmacol. 2009;29:307-310. 3. Chen CY, Gerhard T, Winterstein AG. Determinants of initial pharmacological treatment for youths with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol.2009;19:187-195. 4. Turgay A. Psychopharmacological treatment of oppositional defiant disorder. CNS Drugs. 2009;23:1-17.