Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care Kelly McGuire, MD, MPA,a,b Lawrence K. Fung, MD, PhD,c Louis Hagopian, PhD,d Roma A. Vasa, MD,e Rajneesh Mahajan, MD,e Pilar Bernal, MD,f Anna E. Silberman, MS,a Audrey Wolfe, MPH,g Daniel L. Coury, MD,h Antonio Y. Hardan, MD,c Jeremy Veenstra-VanderWeele, MD,a,i Agnes H. Whitaker, MDa abstract OBJECTIVE: Pediatric primary care providers (PCPs) caring for patients with autism spectrum disorder (ASD) often encounter irritability (vocal or motoric outbursts expressive of anger, frustration, or distress) and problem behavior (directed acts of aggression toward other people, self, or property). The Autism Intervention Research Network on Physical Health and Autism Speaks Autism Treatment Network charged a multidisciplinary workgroup with developing a practice pathway to assist PCPs in the evaluation and treatment of irritability and problem behavior (I/PB). METHODS: The workgroup reviewed the literature on the evaluation and treatment of contributory factors for I/PB in ASD. The workgroup then achieved consensus on the content and sequence of each step in the pathway. RESULTS: The practice pathway is designed to help the PCP generate individualized treatment plans based on contributing factors identified in each patient. These factors may include medical conditions, which the PCP is in a key position to address; functional communication challenges that can be addressed at school or at home; psychosocial stressors that may be ameliorated; inadvertent reinforcement of I/PB; and co-occurring psychiatric conditions that can be treated. The pathway provides guidance on psychotropic medication use, when indicated, within an individualized treatment plan. In addition to guidance on assessment, referral, and initial treatment, the pathway includes monitoring of treatment response and periodic reassessment. CONCLUSIONS: The pediatric PCP caring for the patient with ASD is in a unique position to help generate an individualized treatment plan that targets factors contributing to I/PB and to implement this plan in collaboration with parents, schools, and other providers.

a Department of Psychiatry, Columbia University Medical Center and New York State Psychiatric Institute, New York, New York; bCenter for Autism and Developmental Disorders, Maine Behavioral Healthcare, South Portland, Maine; cDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California; Departments of dBehavioral Psychology and ePsychiatry, Kennedy Krieger Institute, and Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland; fPsychiatry, Children’s Health Council, Palo Alto, California; gMassGeneral Hospital for Children, Boston, Massachusetts; hNationwide Children’s Hospital, Columbus, Ohio; and iNew York Presbyterian Hospital Center for Autism and the Developing Brain, White Plains, New York

Dr McGuire contributed to the design of the practice pathway, played a leading role in drafting the initial manuscript, and revised the manuscript; Drs Fung, Hagopian, Vasa, Mahajan, Bernal, and Coury and Ms Silberman and Ms Wolfe contributed to the design of the practice pathway and reviewed and revised the manuscript; Drs Hardan and Veenstra-VanderWeele contributed to the conceptualization and design of the practice pathway and reviewed and revised the manuscript; Dr Whitaker played a leading role in conceptualizing and designing the practice pathway, drafted portions of the initial manuscript, and reviewed and revised the manuscript; and all authors approved the fi nal manuscript as submitted.

To cite: McGuire K, Fung LK, Hagopian L, et al. Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care. Pediatrics. 2016;137(S2):e20152851L

Downloaded from www.aappublications.org/news by guest on October 1, 2021 SUPPLEMENT ARTICLE PEDIATRICS Volume 137, Number S2 , February 2016 :e 20152851 Autism spectrum disorder (ASD) functioning, or relationships. Atypical psychologist (L.H.) to revise and is a neurodevelopmental disorder neuroleptics have become widely refine the initial pathway draft. The characterized by persistent deficits used in patients with ASD10 but carry workgroup reviewed the literature in social communication and a significant risk of metabolic11 and on assessment and treatment of interaction as well as restrictive, neurologic adverse events.9,12 These contributory factors for I/PB in ASD repetitive patterns of behavior.1 The concerns mandate consideration and grouped them into 5 domains: important role of pediatric primary of lower-risk interventions, even co-occurring medical conditions, care providers (PCPs) in the care of for severe I/PB, targeting other lack of functional communication, children with ASD is increasingly factors, such as medical problems psychosocial stressors, maladaptive recognized.2 The comprehensive or communication challenges that reinforcement patterns, and care or medical home model for the have been identified as potentially co-occurring psychiatric conditions. care of ASD includes management contributory to I/PB in the individual In each domain, the evidence on of mental health and behavioral patient. assessment and treatment was problems, which are far more not, by itself, sufficient to lead to To provide guidance for the prevalent in children with ASD3 recommendations; therefore, the pediatric PCP, the Autism Speaks than in those without ASD and, if not workgroup achieved consensus on Autism Treatment Network (ATN) addressed, may become increasingly the content and sequence of each Psychopharmacology Committee,13 chronic and disabling.4 Two types step in the pathway, focusing on with input from the parent of presenting problems in ASD can the assessment and treatment of member and clinicians, charged be particularly challenging: severe these behaviors in ASD by pediatric the Irritability Workgroup with irritability and problem behavior. PCPs. Recognizing that primary care developing a practice pathway for For the purposes of this article, settings and available resources the individualized management of the term irritability refers to vocal may vary regionally, the pathway I/PB in the patient with ASD. As the and motoric outbursts expressive was developed to include points medical professionals whom children of anger, frustration, and distress; at which the PCP may want to with ASD will probably encounter these outbursts are often referred to consider referrals to specialists and first and most frequently, pediatric by caregivers as “temper tantrums,” collaboration with the school and PCPs need a breadth of knowledge to “meltdowns,” or “rages.” The term community providers. The pathway enable them to identify contributing problem behavior refers to directed also highlights situations in which factors to I/PB, decide when and how acts of aggression that have a high the workgroup agreed that use of to initiate treatment, and judge when potential to or do result in harm atypical neuroleptics is clinically to refer to specialists. Therefore, to other people, self, or property. indicated. The workgroup paid this practice pathway can be viewed Irritability and problem behavior close attention to operationalizing more as a comprehensive rather than (I/PB) are considered as a single the monitoring of treatment and an exhaustive recommendation for topic here because they commonly, reassessment intervals. PCPs, who must weigh their expertise but not invariably, co-occur in and resources when addressing the At 3 points in the development of ASD5 and because many treatment range of issues that a child with ASD the practice pathway, members research studies use measures and I/PB may present. of the workgroup interviewed that aggregate I/PB.6 Importantly, outside consultants with respect to I/PB can jeopardize educational each element of the pathway. First, and recreational placements and METHODS expert advice was sought for the key even lead to inpatient psychiatric domains of evaluation and initial hospitalization7 or residential Using an iterative process, the structure of the pathway before placement.8 Irritability Workgroup met regularly development of the narrative. Second, (weekly to monthly as needed) to a refined draft of the pathway and As presented by Fung and colleagues9 achieve consensus on definitions of the initial narrative were reviewed. in this issue, meta-analysis of irritability and problem behavior In the last review, a near-final draft controlled trials confirms the efficacy and to develop the pathway. The of the pathway, narrative, and of 2 atypical neuroleptics, risperidone workgroup consisted primarily accompanying article were refined. and aripiprazole, approved by the US of child psychiatrists from 6 Food and Drug Administration for the current and former ATN sites management of “severe irritability” (K.M., L.K.F., R.A.V., R.M., P.B., J.V., RESULTS based on clinical trials in children A.Y.H., and A.W.), with additional with ASD who have frequent I/PB participation from a developmental Figure 1 is a visual presentation that is interfering with development, pediatrician (D.L.C.) and behavioral of the practice pathway. Table 1

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 137 , number S2 , February 2016 S137 FIGURE 1 I/PB in ASD: A practice pathway for pediatric psychiatry.

Downloaded from www.aappublications.org/news by guest on October 1, 2021 S138 MCGUIRE et al TABLE 1 I/PB in ASD: Detailed Practice Pathway for Pediatric Primary Care Step Details 1 □ Assess for I/PB. Has this patient recently shown: If yes, how much of a problem? Safety risk? Tantrums, meltdowns, rages? No □ Yes □ None □ Mild–Moderate □ Severe □ No □ Yes □ Property destruction? No □ Yes □ None □ Mild–Moderate □ Severe □ No □ Yes □ Aggression to others? No □ Yes □ None □ Mild–Moderate Severe □ No □ Yes □ Self-injury? No □ Yes □ None □ Mild–Moderate Severe □ No □ Yes □ 2 □ Assess safety. Has patient ever been aggressive to others or engaged in self-injurious behavior? No □ Yes □ Has patient ever caused tissue damage to self or others? No □ Yes □ If yes, accidental? No □ Yes □ Is patient at imminent risk of injuring self or others at home or in other settings? No □ Yes □ If yes, is the family in crisis (unable to cope with managing the patient’s behavior)? No □ Yes □ Enlist home-based crisis services and consider partial or inpatient hospitalization. Is patient at risk now of hurting self or others in the offi ce? No □ Yes □ If yes, and if the patient has a history of I/PB and safety concerns outweigh risk of another escalation, consider safe escort to an emergency department. Notify the emergency department in advance of special needs. If safety permits, proceed with the practice pathway. 3 □ Review the patient’s history and level of functioning before and after the onset of I/PB. History Medical: Genetic disorder, preterm birth, epilepsy, brain injury, typical stooling pattern, chronic medical problems, as well as all medications and supplements taken Take lifetime history of all medication and, for psychotropic medications, obtain dosages, duration of treatment, and blood levels (when applicable) Developmental: Global delay or intellectual disability, specifi c learning disability, developmental age and adaptive functioning versus chronological age, toilet training, motor problems, sensory defi cits and sensitivities Communication: Means of communication (verbal, sign or modifi ed sign, communication tools), indicators of pain, means of learning new information, ability for functional communication Psychiatric: Previously diagnosed psychiatric disorder (eg, anxiety disorders including obsessive–compulsive disorder, ADHD, mood and psychotic disorders), treatments, activity level, preoccupations, special interests, stereotypies, transition problems, social reciprocity, typical responses of care providers to I/PB Current context Settings: Home (family home, group home in community, group home institutional, hospital), school (mainstream no accommodations, mainstream with accommodations, mainstream with resource, full inclusion, partial inclusion, self-contained special education, home instruction, early intervention at home, center) Caretaker characteristics: Two parents, single parent, foster, adoptive; primary language, ethnicity, recently immigrated psychiatric history, number of children in home, number of adults in home, case manager Functioning before and after onset of I/PB Loss of skills: Does the patient no longer exhibit skills used on a regular basis before onset of I/PB? No □ Yes □ Interference with self-care and functioning at home □ learning and participation at school or program □ travel in public or out in the community □ acceptance by peers □ family and caregiver relationships 4 □ Prioritize for assessment and treatment on the basis of safety, severity, and impact on daily life □ Qualify I/PB target behaviors: acute or chronic, frequency and severity, episodic or continuous, discrepancy in behaviors across settings (eg, infl uenced by environment, caretaker, and task). □ Specifi cally assess for property damage or injury to self or others. □ Know how incidents have been handled and what has happened as a result. 5 □ Consider all potential contributors to I/PB. 5a □ Assess and address any current medical problems. □ Conduct a medical review of systems. □ Treat any pain, seizures, sleep, GI, ear/nose/throat, dental problems, or other medical conditions. Monitor I/PB after medical treatment is applied to determine whether problems may have been secondary to a medical condition. □ Consider the possibility of medications being responsible for I/PB. □ When a medication is suspected, consider stopping, decreasing, or switching to another agent in discussion with the prescribing provider or consulting with a colleague experienced in psychopharmacology in developmental disabilities, particularly when a patient is taking multiple medications. 5b □ Assess and address diffi culties using functional communication: Evaluate the level of patient’s functional communication skills and whether I/PB may be related to diffi culties communicating. If yes: □ Make appropriate referrals for a speech and language evaluation to ensure incorporation of an adequate and functional communication system consistently across settings. □ Make appropriate referrals to psychologist or behavior analyst to include a communication component in a behavior treatment plan.

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 137 , number S2 , February 2016 S139 TABLE 1 Continued Step Details 5c □ Assess and address any psychosocial stressors. □ Physical or sexual abuse. If yes: Consider specialist referral, contacting child protective services. □ Bully victimization. If yes: Consider 504 accommodations in school to avoid exposure. □ Parental stress. If yes: Consider referrals for fi nancial or psychological assistance. □ Poor match between the patient and his or her psychosocial context □ Classroom or program characteristics. If yes: □ Request classroom program change. □ Family characteristics. If yes: □ Consider parent training or other referrals. 5d □ Assess and address any maladaptive reinforcement patterns. □ Are there triggers for I/PB? Do caregivers react in a manner that may inadvertently reinforce I/PB? If yes: □Advise caregivers on how to respond to I/PB accordingly. If problems persist or are severe: □ Make appropriate referrals to a psychologist or behavior analyst with specialization in functional behavioral assessment and treatment of I/PB. 5e □ Assess and address any co-occurring psychiatric disorders. □ Screen for co-occurring psychiatric disorders (in ASD most commonly anxiety, ADHD, obsessive–compulsive, mood and psychotic disorders). □ For any screen-positive disorders (or others suspected), conduct or refer for more detailed diagnostic assessment. □ As indicated, treat or refer for treatment of any co-occurring disorders with medications. □ Cognitive–behavioral therapy conducted by a mental health provider with necessary expertise. 6 □ Consider psychopharmacologic interventions for I/PB. □ When there is no current risk to safety or loss of educational placement, consider N-acetylcysteine and clonidine. □ Under the following circumstances, consider risperidone or aripiprazole: □ Safety is an issue. □ Change in an otherwise satisfactory education or school placement will be necessary without treatment. □ Other indicated interventions have resulted in no or incomplete improvement of behavior that continues to interfere with daily function. □ I/PB is judged to be unrelated to medical conditions, communication diffi culties, psychosocial stressors, or maladaptive reinforcement patterns or □ Lower-risk interventions cannot be implemented. 7 □ Develop the individualized treatment and safety plan: Coordinate an individualized treatment plan for patient based on information gathered from steps 5a–5e, taking preferences of care providers and feasibility of implementation into account. 8 □ Implement and monitor the treatment plan: After beginning to implement treatment plan, monitor with regular visits based on the severity and frequency of the I/PB behavior. □ Clear and measureable treatment goals should be established. □ Carefully track response to intervention as determined by report of caregivers, direct observation, and objective rating scales, such as the ABC or longitudinal behavioral data from the school or home setting. □ Expect improvements within 4–8 wk. 9 □ At 3 mo do symptom(s) persist? If yes: Restart assessment and revise treatment plan. 10 □ Reevaluate every 3 mo thereafter. □ Enrich positive behavioral support plan and address quality of life goals. □ After a 12-mo symptom-free period, consider tapering or discontinuing any medications used for the treatment of I/PB behavior. □ Positive behavioral supports, communication aides, and psychosocial supports should be left in place. provides more detail on each step as to whether any I/PB has occurred interferes with learning, functioning, of the pathway, and the narrative recently or since the last visit and relationships, or poses a risk provides a summary of the literature (Table 1). Accord more weight to to safety. I/PB may be regarded as and clinical rationale for each step. caregiver descriptions than to office mild to moderate when it occurs Supplemental Table 2 provides observations because the medical more frequently than in peers but information about measures office is a nonroutine setting that only intermittently disrupts learning, potentially useful in primary care. may elicit atypical reactions from functioning, and relationships and The pathway assumes that the the patient (eg, unusual withdrawal does not pose a safety risk. Even diagnosis of ASD is not in question or agitation). If office staff are aware when only mild to moderate, I/PB and that the child is ≥3 years old. The that I/PB is among the reasons must still be assessed and addressed Autism Speaks Challenging Behaviors prompting the visit, scheduling to prevent the I/PB from becoming Tool Kit can be helpful in discussing the patient’s appointment so as to more entrenched, difficult to treat, I/PB with a family for the first minimize waiting time and sending and potentially unsafe. time (https:// www. autismspeaks. relevant forms to the caregiver to Step 2. Assess Safety org/ family- services/ tool- kits/ complete in advance can be helpful. challenging- behaviors- tool- kit). Based on caregiver and school or For clinical purposes, I/PB may be program reports, assess whether the Step 1. Assess for I/PB considered severe when it occurs patient is at imminent risk of doing Because I/PB is so prevalent in more frequently in the patient than harm to self or others. If so, this patients with ASD, inquire routinely in peers in the same setting, regularly acute situation warrants immediate

Downloaded from www.aappublications.org/news by guest on October 1, 2021 S140 MCGUIRE et al intervention. With knowledge of the significance of I/PB, to set history of medical problems.17 Focus the family and patient, the PCP attainable goals, and to monitor on current signs and symptoms is in a unique position to assess response.16 The comparison of and review all current and recently whether the family is in crisis, which current functioning with that before discontinued medications and happens when the demands of the onset of I/PB can be a good supplements. A complete, rather the behavior exceed their present indicator of the possible impact than a targeted, review of systems ability to cope.14 In some states, on learning and maintenance of may be necessary, especially when crisis services for patients with previously acquired skills. the child is nonverbal. The physical developmental disabilities or mental examination should be thorough health conditions can be called on Step 4. Prioritize and Qualify Specifi c because children with ASD may to provide acute interventions (eg, Behaviors for Treatment be unable to localize symptoms or in-home behavioral management In the case of >1 problem behavior describe them in words.16,18 Children or respite) to support the patient (eg, aggression and property with ASD commonly experience and family in the community destruction), prioritize for treatment all of the usual childhood illnesses while admission to more intensive based on the threat to safety and and problems, although they services (eg, partial or inpatient severity, as defined in Step 1. may present differently in a child hospitalization) is being considered, Aggression toward other people who cannot describe symptoms. preferably to a program or unit or self-injurious behaviors require Recent reviews describe behaviors that has staff trained to serve this priority. Frequent tantrums can also indicative of gastrointestinal (GI) population. seriously affect child and caregiver dysfunction19 and dental orofacial pain20 in children with ASD. A recent Severe I/PB that is sometimes well-being and may also represent case series suggests that addressing exhibited in the office setting precursor behaviors to aggression concomitant painful or distressing often reflects a fear reaction and that represent a more realistic medical conditions in patients impulse to flee or to fight. Whenever starting point for treatment. with ASD and acute or severe I/ possible, avoid physical restraint, All available sources should be PB predicts enhanced response to avoid excessive talking that may used to obtain a detailed history of treatment.21 overwhelm the patient’s verbal the specific behaviors that will be abilities, use visuals or concrete addressed and monitored during language, and direct the patient Sleep Problems: Sleep problems treatment. For each behavior, to a dimly lit, quiet, safe space, if occur more frequently in patients establish when it began, whether available. Consider escort to an with ASD than in typically the onset was sudden or insidious, emergency department only if the developing patients and are as well as where and when the patient does not calm down and strongly associated with daytime concerning behaviors happen has a history of I/PB and if the I/PB, among other problems.22 most frequently. Inquire as to how need for safety outweighs the risk Although more research is needed, caregivers in different settings of escalation in the emergency many clinicians have anecdotal typically respond to the behavior and department. If possible, notify the experience with improvement how the patient behaves if caregivers emergency department in advance so in I/PB after treatment of sleep do not provide their typical response. that staff can prepare for the patient’s problems.22 Promotion of sleep Obtain details about whether the special needs. hygiene in children with sleep behavior is episodic or continuous, its 23 frequency and typical duration, and problems should be prioritized. Step 3. Review the Patient’s History what, if anything, seems to trigger the The ATN has a useful packet to help and Level of Functioning Before and behavior. These parameters will form parents improve their child’s sleep After the Onset of I/PB the basis of monitoring response to habits (https://www. autismspeaks. Review the patient’s developmental, treatment, regardless of modality. org/science/ resources- programs/ autism-treatment- network/ tools- medical, and psychiatric history, Step 5. Consider All Potential as well as caretaker and home Contributors to I/PB you-can- use/ sleep- tool- kit). A recent environment characteristics.2,15,16 systematic review and meta-analysis Information on the patient’s Step 5a. Assess and Address Any of melatonin treatment in ASD found Current Medical Problems typical level of functioning significant improvements in sleep (eg, adaptive skills, academic A contribution of medical conditions duration and sleep onset latency performance) before onset of I/ to I/PB should be strongly but not in nighttime awakening.24 PB, and functioning since the onset considered if the behaviors are Nighttime awakening may be a of I/PB, is needed to interpret new in onset or the child has a past sign of a variety of conditions,

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 137 , number S2 , February 2016 S141 including primary sleep disorder of motor restlessness that can facilitate appropriate expressive (eg, parasomnias, circadian rhythm be abrupt or insidious, may communication interventions.16 As sleep–wake disorders), co-occurring fluctuate during the day, and indicated, specific communication medical conditions (seizures, sleep typically affects the lower strategies (Picture Exchange apnea, gastroesophageal reflux), or extremities. Several prescription Communication System, sign psychiatric disorder (particularly medications, including stimulants, language) or augmentative and mood disorders). These conditions phosphodiesterase inhibitors, alternative communication devices may need specialist evaluation and muscle relaxants, and a number (dedicated devices and tablet apps35), treatment of their own sake. of antiepileptic medications, can and literacy instruction36 should be GI Dysfunction: A recent meta- increase irritability, decrease considered. analysis found a higher prevalence impulse control, or adversely Step 5c. Assess and Address Any of GI symptoms among children affect mood. Serotonin reuptake Psychosocial Stressors with ASD compared with pediatric inhibitors and benzodiazepines can cause disinhibition or controls, particularly diarrhea, Abuse: Children with developmental behavioral activation that can constipation, and abdominal disabilities are at elevated risk present as I/PB. Antihistamines pain.25 A recent study documents of physical and sexual abuse.37,38 and other medications with a relationship between GI Both types of abuse are associated anticholinergic properties symptoms and irritability in with problem behavior.38 Based can cause confusion or frank children with high-functioning on knowledge of the patient and delirium that leads to I/PB. Other ASD.26 Recommendations for family, the PCP is in the best position over-the-counter medications, the evaluation and treatment of to differentiate accidental injury such as pseudoephedrine common GI problems in the ASD from deliberately inflicted tissue or dextromethorphan, and population are available.19 Expert damage that is due to abuse, the complementary and alternative clinical consensus suggests that latter necessitating involvement medicines, may also trigger acute treating GI problems can lead to of protective services. People with behavioral changes. Importantly, improvement in I/PB,19 but more ASD are more vulnerable to being abrupt withdrawal of medication research is needed. sexually abused or victimized.39 The can also trigger I/PB.2,16,30 Epilepsy and Epileptiform assessment of possible sexual abuse Abnormalities: A recent review27 When present, specific treatment of in the child with ASD can be complex describes the complex relationship any medical or medication-related and, absent clear-cut evidence on between epilepsy, epileptiform problems should be added to the physical examination, involves abnormalities on EEG, and behavior treatment plan. consideration of multiple factors in ASD. Studies using rigorous often necessitating the expertise of 40 diagnoses of ASD and behavioral Step 5b. Assess and Address Diffi culties colleagues specializing in that area. Through Functional Communication measures are rare. A recent small Bully Victimization: Elementary case series of children with ASD and The patient with ASD who lacks and middle school students with epileptiform abnormalities found no a functional communication ASD are at higher risk for repeated difference in I/PB between patients system may exhibit I/PB as a bully victimization than children with and without EEG abnormalities, manifestation of frustration or as having other disabilities, which may but those with seizures had a means of communication.31,32 I/ actually be a bigger problem for significantly worse I/PB than their PB may rapidly diminish when the higher-functioning children who are 28 peers without seizures. As noted patient is provided with a more more mainstreamed at school.41,42 9 29 by Fung et al and others, evidence efficient and effective system Few studies have been conducted that anticonvulsants diminish I/PB is of communicating.33,34 If the on this topic, but 1 cross-sectional inconsistent. patient does not have consistent study found that victimization Medication Side Effects: Children access to and use of an adequate was associated with internalizing with ASD can be sensitive to communication system across problems (anxiety, depression) in psychoactive medications, which settings, the treatment plan should children with ASD.43 The PCP can are sometimes responsible for I/ include evaluation by a speech help identify this problem for the PB.2,16,30 For example, first- or language pathologist, either in school and advocate for interventions second-generation neuroleptics the school as part of the child’s to prevent bullying. Importantly, and selective serotonin reuptake Individualized Education Program not all negative peer experiences inhibitors can cause akathisia, or in the community setting by result from bullying, and social a subjectively unpleasant sense medical referral, to identify and isolation and more subtle forms of

Downloaded from www.aappublications.org/news by guest on October 1, 2021 S142 MCGUIRE et al peer rejection can also be significant activity. Functional behavioral how to create a well-structured, stressors. assessment of I/PB is designed to engaging environment. When identify variables that occasion necessary, referral should be Parental Stress: A recent and maintain I/PB symptoms made to an experienced behavior longitudinal study found that (as reviewed4,49–51). The most analyst or mental health expert parental general distress related commonly reported behavioral for comprehensive functional to parenting a child with special functions for I/PB include access behavior assessment in the home.16 needs predicts tantrums, aggression, to attention, access to tangible If these behaviors occur at school, noncompliance, and self-injurious rewards, escape from tasks or collaboration and coordination behavior (among other behavior demands, and apparent sensory with the school are encouraged. problems), with only modest reinforcement (inferred when these Specifically, PCPs can inform evidence of a bidirectional behaviors occur across situations parents and the school that a form relationship.44 Participation in independent of consequences). of functional behavior assessment psychoeducational, supportive Recent reviews have found that by the school is required by the programs45 may reduce parental behavioral interventions based on 1997 amendments to the Individuals stress and improve mental health.46 understanding of the function of I/ with Disabilities Education Act The PCP can help support parents in PB are highly effective in producing for students who exhibit problem distress, including linking them to a consistent decrease in aggressive behavior at school in the United ASD support groups and referring or self-injurious behavior in States.53 Behavioral interventions them to get help for their own ASD.49,51 Even without changing emerging from functional mental health needs.47 the response to the behavior itself, assessments should be added to the Poor Match Between the specific events and antecedents treatment plan. These will typically Environment and the Patient: that commonly precede I/PB, such emphasize removing inadvertent A different type of psychosocial as unstructured times or transition reinforcement and teaching socially stressor can arise when the home, from preferred to nonpreferred appropriate replacement behaviors. school, or other environment does activity, can often be addressed not provide sufficient structure or by using environmental supports Step 5e. Assess and Address Any fails to meet the emotional needs of and introducing structure such as Co-occurring Psychiatric Disorders the child based on developmental visual schedules or predictable Co-occurring psychiatric disorders age, leading to chronic frustration, routines. Additional detail on are highly prevalent in ASD. manifested as I/PB.48 An example functional behavior analysis Irritability is a core or associated would be the patient with ASD who and treatment is provided at clinical feature of many psychiatric is verbal and placed in a classroom http://www. kennedykrieger. disorders and may be the primary with mostly nonverbal classmates, org/patient- care/ patient- care- presentation of such disorders in or vice versa. The PCP can be an programs/inpatient- programs/ patients with ASD, particularly those important advocate for the patient in neurobehavioral-unit- nbu/ applied- who are nonverbal. Therefore, a drawing the attention of parents and behavior-analysis. The ATN has also psychiatric differential diagnosis of educators to this kind of mismatch developed a guide for parents on I/BP is in order whenever a patient and asking them to consider applied behavior analysis (https:// presents with new onset or markedly a different, more appropriate www.autismspeaks. org/ science/ worsened I/PB. The disorders to placement. resources-programs/ autism- be considered include those known treatment-network/ atn- air- p- to occur at elevated rates in ASD: Step 5d. Assess and Address Any applied-behavior- analysis). attention-deficit/hyperactivity Maladaptive Reinforcement Patterns disorder (ADHD), anxiety disorders, In many cases, I/PB is occasioned PCPs can often identify what events and obsessive–compulsive disorder, by events in the environment precede and what consequences which typically present first in and serves a specific reinforcing follow I/PB, based on interviews of childhood, as well as episodic mood function for the patient. For parents or care providers.52 Even disorders (depression and mania) example, problem behaviors may without a specific understanding that typically begin in adolescence be triggered when the patient of antecedents and consequences, or early adulthood.54 Importantly, is presented with a difficult PCPs can educate care providers although the newly described task. This behavior might then about general and basic behavioral Diagnostic and Statistical Manual of become reinforced if the care management techniques, including Mental Disorders, Fifth Edition (DSM- provider gives the patient a break reinforcement of positive 5) diagnosis of disruptive mood or redirects him to a different behaviors, and guidance on dysregulation disorder1 includes

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 137 , number S2 , February 2016 1 S143 core behaviors of severe, recurrent capabilities. With regard to other Given the risks and benefits, atypical temper outbursts and persistent psychiatric disorders, it is reasonable neuroleptics such as risperidone irritable mood, this diagnosis should to adapt treatments with evidence in and aripiprazole therefore should rarely, if ever, be diagnosed in the general pediatric population.58–60 be used to treat severe I/PB in ASD patients with ASD because the DSM-5 If medications are used, it is important only in the following situations: specifies that it does not apply when to recognize that adverse events are safety is an issue; the behaviors symptoms are better explained by likely to be more common in ASD, interfere with current functioning another disorder, including ASD. As including activation and disinhibition to the degree that a change in with co-occurring medical conditions, from serotonin reuptake inhibitors61 school or residential placement will treatment of any co-occurring and irritability from stimulants,62 so be necessary without treatment; psychiatric disorder in the patient “start low and go slow.” other indicated interventions with ASD is indicated both because have resulted in no or incomplete it may directly diminish I/PB and improvement of behavior that because it may enhance response to Step 6. Consider continues to interfere with daily Psychopharmacologic Interventions other interventions, as suggested by function; I/PB is judged to be for Severe I/PB a recent case series of psychiatric unrelated to psychosocial stressors, inpatients with ASD.21 In most cases, targeted communication difficulties, psychopharmacologic interventions underlying medical or psychiatric Assessment for co-occurring for I/PB should be considered conditions, or environmental psychiatric disorders should account only after any contributing factors factors; or lower-risk interventions for the child’s intellectual and are assessed and addressed. In cannot be implemented. Families communicative abilities, symptoms the case of severe I/PB that is sometimes struggle with the choice typical of ASD, and developmentally acutely or imminently unsafe, of whether to use medication for normative behaviors.16,30 Depending targeted psychopharmacologic their child, and the ATN Medication on local options, evaluation and intervention should be considered Decision Aid can help PCPs and treatment of other co-occurring even while contributing factors are families work together to weigh the psychiatric disorders are often being evaluated. In a systematic potential benefits and risks (https:// referred to a mental health expert review of the efficacy and safety www.autismspeaks. org/ science/ experienced in ASD, with the of pharmacologic treatments for resources-programs/ autism- exception of ADHD. Most PCPs have severe I/PB in children with ASD, treatment-network/ tools- you- can- experience managing ADHD in the risperidone and aripiprazole had use/medication- guide). general pediatric population and can the strongest evidence in reducing refer to the ATN practice pathway Aberrant Behavior Checklist As noted by Fung et al,9 single studies for guidance regarding evaluation Irritability Subscale (ABC-I) scores, of N-acetylcysteine and clonidine and choice of medications, primarily but with adverse effects including showed significant efficacy in including stimulants and α-agonists, somnolence or sedation, weight reducing ABC-I scores and did not in the ASD population.55 In other gain, and extrapyramidal symptoms cause significant side effects in the circumstances, PCPs may be called such as tremor, dyskinesia, areas assessed. Although replication on to manage other psychiatric akathisia, and rigidity.9 Additional of these studies is needed to confirm disorders when a referral is not adverse effects of the neuroleptics the findings, N-acetylcysteine and immediately available, in which case mentioned earlier include clonidine might be considered for they should refer to the literature urinary retention, constipation, treatment of I/PB in ASD when regarding special considerations insulin resistance, dyslipidemia, atypical antipsychotics are deemed in the assessment and treatment hyperprolactinemia, hematologic inappropriate. of psychiatric disorders in children abnormalities, QTc prolongation, with ASD (see for a review30,56). seizures, and neuroleptic malignant Step 7. Develop the Individualized Unfortunately, outside of ADHD there syndrome. These potential adverse Treatment and Safety Plan is little evidence for treatment of effects must be monitored closely co-occurring psychiatric disorders with frequent follow-up, laboratory The treatment plan for I/PB should in ASD. One exception is data testing, electrocardiogram, address the individual needs of supporting cognitive behavioral and assessment for movement the patient with ASD based upon therapy for anxiety disorders57; disorders.63 Ameis and colleagues63 an evaluation of all potentially however, this specialized treatment provided a more detailed contributory factors. With rare may not be broadly available and discussion of monitoring of atypical exception, the treatment of must be adapted to the individual’s neuroleptics in ASD. potentially contributory medical

Downloaded from www.aappublications.org/news by guest on October 1, 2021 S144 MCGUIRE et al or psychiatric conditions should and, as needed, with phone DISCUSSION be a top priority because if left contact between visits. Carefully The pediatric PCP is in an important untreated or undertreated, these track response to intervention. position to identify and initiate conditions may interfere with other Treatment response should be treatments for I/PB in the patient interventions. The individualized determined by caregiver report with ASD independently or in treatment plan will also take account and direct observation of the collaboration with other providers. of factors that may limit the ideal behavior by teachers or other No other provider in the patient’s treatment plan (eg, limited access providers. Objective rating life combines the medical expertise 66 to specialists, insurance problems, scales, such as the ABC, or and first-hand knowledge of the and limited family resources for longitudinal behavioral data based individual patient’s health and implementing the plan). on observations in the school or development. The practice pathway home setting can help determine As per the 2007 American Academy is most likely to be efficient and effectiveness of treatment. of Pediatrics report,2 PCPs should effective in generating a treatment Clear and measurable treatment prescribe only psychotropic plan if it is systematically followed goals should be established medications with which they have and the specific combination of (eg, reduction in frequency of sufficient expertise, including individual contributing factors aggressive outbursts by a specific knowledge of indications and is identified for each patient. number or reduction in duration contraindications, dosing, Importantly, evaluation and of outbursts by a specific time). potential adverse effects, drug– individualized treatment of I/PB, as If atypical neuroleptics are drug interactions, and monitoring outlined in the practice pathway, are to be used, the guidelines for requirements. When consultation an iterative process that may require monitoring presented by Ameis is needed, telephone consultation an extended initial visit and will and colleagues63 can be useful. services such as the Massachusetts probably be refined over subsequent Child Psychiatry Access Project are visits. available in some states.64 Primary Step 9. At 3 Months, Do Symptoms of I/PB Persist? Inasmuch as this practice pathway care clinicians have found these is necessarily broad in its scope, it services helpful in supporting Some benefit and improvement is limited in its detail. The pathway management in the primary should be expected within ~4 draws on different aspects of care setting. Before embarking to 8 weeks; however, a longer treatment models proposed for on treatment, it is important to time window may be necessary people with developmental or work with the family to develop to track less frequent behavior. intellectual disabilities such as an emergency plan that outlines If clinically significant symptoms the neurobehavioral model,67–70 what to do if the child’s behavior persist at 3 months, reassess for which describes the tandem usage suddenly deteriorates during all contributing factors, and revise of psychiatric assessment and treatment and needs immediate the treatment plan. If no clinically applied behavioral analysis for attention. This includes identifying significant symptoms persist at 3 the treatment of severe problem behavioral interventions that may months, continue to enrich positive behavior. A recent article by deescalate the child, administering behavioral support plans and Minshawi et al71 provides a similar medications, calling 911, or address quality of life goals. approach to the treatment of self- going to the nearest emergency injurious behavior, specifically in department.65 Encourage parents to Step 10. Reevaluate Every 3 Months ASD. In contrast with such detailed review this plan with family, other Thereafter reviews, however, the practice caregivers, therapists, and school After a symptom-free period of pathway presented here is designed staff. In situations where I/PB are ≥12 months, consider gradually to assist PCPs with initiating and severe, the local police department tapering or discontinuing any coordinating interventions in the should also be informed of psychotropic medications used for primary care setting. Although this the child’s ASD diagnosis and treatment of I/PB. Importantly, it is pathway has not yet been tested behavioral risk to allow response advisable to wait for a stress-free in the primary care setting, the preparation. period to do this, even if this means balance of evidence and clinical prolonging medication treatment consensus that informs this Step 8. Implement and Monitor the past 12 months. Positive behavioral pathway supports the premise that Treatment Plan supports, communication aides, and careful multifactorial assessment This step should occur at least psychosocial supports should be left and treatment planning maximize monthly during office visits in place. the efficiency and effectiveness

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 137 , number S2 , February 2016 S145 of treatment for I/PB while in collaboration with parents, minimizing risks for the individual schools, and other providers. ABBREVIATIONS patient. ABC: Aberrant Behavior Checklist ADHD: attention-deficit/ ACKNOWLEDGMENTS hyperactivity disorder CONCLUSIONS ASD: autism spectrum disorder The authors thank the following ATN: Autism Treatment Network The pediatric PCP caring for consultants for helpful comments DSM-5: Diagnostic and Statistical the patient with ASD and I/ on the practice pathway at Manual of Mental PB is in a unique position to various points in its development: Disorders, Fifth Edition initiate the development of an Evdokia Anagnostou, MD, Lauren GI: gastrointestinal individualized treatment plan Brookman-Frazee, PhD, Craig I/PB: irritability and problem based on the combination of Erickson, MD, Bryan King, MD, behavior contributory factors in that James McCracken, MD, and PCP: primary care provider patient and implement the plan Matthew Siegel, MD.

DOI: 10.1542/peds.2015-2851L Accepted for publication Nov 9, 2015 Address correspondence to Agnes H. Whitaker, MD, 1051 Riverside Dr, Unit 74, New York, NY 10032. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2016 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: Dr Veenstra-VanderWeele has received research support from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis, and SynapDx; the other authors have indicated they have no fi nancial relationships relevant to this article to disclose. FUNDING: Supported by the Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services (HHS) under cooperative agreement UA3 MC11054, Autism Intervention Research Network on Physical Health. This information or content and conclusions are those of the authors and should not be construed as the offi cial position or policy of, nor should any endorsements be inferred from, the HRSA, HHS, or the US government. Conducted through the Autism Speaks Autism Treatment Network, serving as the Autism Intervention Research Network on Physical Health. Funding was also provided by Marilyn and James Simons Family Giving (Drs McGuire, Siberman, and Whitaker). POTENTIAL CONFLICT OF INTEREST: Dr Veenstra-VanderWeele has received research support from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis, and SynapDx; the other authors have indicated they have no potential confl icts of interest to disclose.

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