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Autism Disorder: Parents’ Guide Parents’ Medication Guide Work Group CO-CHAIRS: Matthew Siegel, MD and Craig Erickson, MD, MS

MEMBERS: Jean A. Frazier, MD Toni Ferguson, Autism Society of America Eric Goepfert, MD Gagan Joshi, MD Quentin Humberd, MD Bryan H. King, MD, Representative to the American Psychiatric Association Amy Lutz, EASI Foundation: Ending Aggression and Self-Injury in the Developmentally Disabled Louis Kraus, MD, Representative to the American Psychiatric Association Alice Mao, MD Adelaide Robb, MD Jeremy Veenstra-VanderWeele, MD, PhD Paul Wang, MD,

STAFF: Carmen J. Head, MPH, CHES, Director, Research, Development, & Workforce

CONSULTANT: Eve Bender, Scientific Editor

©2016 American Academy of Child and Adolescent , all rights reserved. Table of Contents

Introduction...... 4

Assessment of the Child with ASD Experiencing Emotional or Behavioral Problems...... 5

Primary Non-Medication Treatment Strategies for Emotional and Behavioral Challenges...... 6

Medication as a Treatment Tool for Emotional or Behavioral Challenges...... 9

Symptoms and ...... 12

Controlled Medication Studies in ASD...... 16

Medication Tracking Form...... 21

References...... 22

Autism : Parents’ Medication Guide 3 Introduction

hat is ASD? Why consider medication in ASD? People disorder (ASD) is a developmental with ASD often experience a host of W disorder characterized by problems difficulties that can be as problematic with social , unusual behaviors as the symptoms of ASD itself. Anxiety, such as fixed interests, being inflexible, having mood instability, impulsivity, hyperactivity, repetitive behaviors, or abnormal responses to sleep problems, and even aggression and sensations. Communication problems include self-injurious behavior can occur in some difficulty understanding and responding to people. Just as it would be for other medical social cues and nonverbal communication problems, medication may be helpful in such as and tone of voice, which treating some of these difficulties. The can result in challenges in making or keeping use of medication is more often aimed at friends. Although people with ASD may want treating the symptoms of these associated to make friends, difficulties in understanding conditions, which we can characterize social norms or correctly interpreting language as emotional and behavioral challenges, and facial expressions can get in the way. than for core symptoms of ASD itself, as no medications have shown clear benefit In recent years, it has become clear that for social communication impairment or individuals with ASD, despite sharing some restricted, repetitive behaviors. behavioral challenges, can be quite different from one another. Some people with ASD Sitting down with an expert to discuss may be very intelligent, while others may have whether it is a good idea to try medication cognitive challenges. Some may have advanced for certain troublesome symptoms in your vocabularies and others may speak very little child with ASD is reasonable. Although or not at all. Previous attempts to subdivide the best approach to addressing those the population on the basis of language and symptoms may not include medication, it cognitive ability have not been supported by can be helpful to learn about various options research. Thus, people in the same family and/or begin to gather information on with autism or who share the same genetic the frequency and intensity of behaviors risk factor(s) can end up with very different that may ultimately be targets for symptoms and outcomes. medication treatment.

4 Autism Spectrum Disorder: Parents’ Medication Guide Assessment of the Child with ASD Experiencing Emotional or Behavioral Problems

hen a challenge presents itself, it providers can assess the functioning of the is time for an assessment. The first family and how family relationships could relate W step in helping a child with ASD to to problems, as well as evaluate for co-existing get assistance with an emotional or behavioral disorders in the child such as challenge is to have him or her evaluated by anxiety or ADHD. and other an expert or team of experts. Since many experts in behavior can assess factors that may factors may contribute to these emotional maintain or reinforce the problem behavior(s), and behavioral problems in a child with ASD, it and can use applied behavioral analysis is ideal to have the child assessed by a team techniques, as outlined below. The possibility whose members can consider different causes of a medical issue underlying the emotional and approaches. In reality, most children will or behavioral symptoms can be assessed by only have access to a single provider, or the a physician or other medical provider. Finally, child’s emotional or behavioral problems are an occupational therapist can assess the role severe enough that there is a need to act of over or under sensitivities and challenges in quickly. Even in these situations, it is important daily living and self-help skills, such as dressing, for the clinician who evaluates the child to bathing, and eating. consider multiple sources for the problem, and refer the child for further assessment if needed.

A thorough assessment of emotional or behavioral problems will take into account the possible role of communication, family functioning, factors that contribute to or exacerbate the behavior, physical health, co-existing mental health disorders, sensory factors, and daily living skills. The child’s ability to communicate should be considered and a speech and language pathologist can perform more formal assessments of language and social communication abilities. Mental health

Autism Spectrum Disorder: Parents’ Medication Guide 5 Primary Non-Medication Treatment Strategies for Emotional and Behavioral Challenges

Applied Behavioral Analysis (ABA) to communicate.2 Electronic assisted As demonstrated in a number of well communication devices include speech designed research studies, Applied Behavioral generating devices (SGD), which can produce Analysis (ABA) has been shown to be an electronic voice that communicates words. effective for addressing and often reducing These SGDs come in two main forms, dedicated challenging behaviors, as well as teaching devices (e.g. DynaVox, AlphaSmart, DynaWriter) many skills and routines. Parents frequently or software (e.g. Proloquo2Go or Touchchat) that have questions about how ABA works and can be used on personal computers, tablets, or how it will help their child. mobile phones.

Children with ASD often have difficulty Speech-language pathologists can recommend learning. Applied Behavior Analysis (ABA) is an assistive communication system after an educational and therapeutic approach that a careful evaluation of the unique abilities, involves breaking down tasks and skills into needs, and communication goals of the their smallest parts, then teaching them slowly child. Preliminary studies have shown that while encouraging, shaping, and reinforcing assistive communication devices are generally functional behaviors and discouraging harmful liked by users and may improve functional or disruptive behaviors. ABA focuses on communication in children with ASD.3 the relationship between a certain behavior, the factors that were present before the Cognitive Behavioral Therapy behavior (“antecedents”) and the results of Cognitive Behavioral Therapy (CBT) is a type the behavior (“consequences”). ABA has been of psychotherapy in which a person’s negative successful in helping children with ASD improve thoughts are challenged in order to reduce are verbal communication, academic performance, social associated troubling emotions and behaviors. behavior, and adaptive living skills as well as CBT is “problem-based,” meaning that it is used and non-verbal 1 addressing specific problem behaviors. to address the specific concerns of a patient. behaviors necessary for CBT has been shown to be an effective treatment positive and effective Communication supports for anxiety in individuals with high functioning While speech is generally the preferred method ASD (HF-ASD), and it may also be helpful in social interactions, and of communication in our society, not all children addressing disruptive behaviors, like aggression, include , with ASD can use speech effectively. For children and in improving social and communication who have limited or no verbal ability, alternative 4 smiling, and asking skills. CBT is typically administered by a methods of communicating have been therapist, but parents and teachers may also and responding developed to improve communication. access books or web-based CBT guides. to questions. Communication supports are tools to help children with ASD communicate. A non- Social Skills/ electronic method that has been shown to Social Cognitive Training increase communication in children with Social skills are verbal and non-verbal behaviors ASD is the Picture Exchange Communication necessary for positive and effective social System (PECS), where the child uses pictures interactions, and include eye contact, smiling,

6 Autism Spectrum Disorder: Parents’ Medication Guide and asking and responding to questions. The value of developed social skills is well-documented and can boost academic performance, mental health, and positive developmental outcomes.5 Social skills training programs are designed to teach the skills necessary to navigate social environments.6 There is also preliminary evidence supporting programs that address social cognitive impairments, such as helping children develop the skill of understanding the perspective of others.7

Life Skills The countless tasks of daily living—including dressing, bathing, mealtimes, homework, free time, toileting, and waiting—present many opportunities for challenging behavior each day. As children become adolescents and young adults, new tasks to learn include keeping their own schedules or appointments, asking for help, caring for their own belongings, preparing meals, navigating transportation, and learning a trade. An occupational therapist and other providers can help establish routines and teach these . By breaking tasks into parts, making visual charts outlining steps, presenting rewards for step completion, and implementing this plan consistently, especially to the shoulders. The evidence caregivers can teach life skills to children Occupational therapists for such interventions is not convincing so with ASD. Before trying to manage far, however, due to problems with study can assess the child’s problem behaviors through other means, consideration should be given to whether methods and research design.Occupational sensory system and direct therapists can assess the child’s sensory the child has adequate support to meet the these interventions to help goals being set for them. system and direct these interventions to help address sensory factors. address sensory factors. Sensory Interventions Possible contributing causes of challenging Treatment of behavior in a child with ASD include Medical Problems to more rare causes. Poor sleep patterns abnormal sensory responses. Children Prior to starting any therapy for a behavioral should be initially addressed with good may avoid sensory input, including certain or emotional problem in ASD, consideration sleep hygiene, such as removing television textures (mushy foods, scratchy labels in should be given to a possible medical and video screens from the bedroom, clothing), excessive movement (crowded cause. The extent of a medical evaluation having a set bedtime and a bedtime routine, and learning to fall asleep without stores, busy city streets), or noises (fire should be decided in collaboration with an a parent present. alarms, barking dogs). They may also seek experienced medical provider. A sudden out sensory experiences, such as tickling or drastic change in behavior may warrant • Medication side effects themselves can or deep pressure, or more frequent and a more thorough evaluation. The medical contribute to problem behaviors. Possible intensive movement, such as running, problems mentioned here do not represent medication side effects include changes climbing, or spinning in circles. Preventing an exhaustive list, but are often causes of in sleep, sedation, cloudiness of thinking, a child’s sensory-seeking or sensory- behavioral problems in children with ASD. constipation, and agitation, among others. avoiding behaviors can cause distress and/ or . Interventions for sensory- • Sleep problems are present in many • When a child experiences pain, yet is related problems include weighted vests, children with ASD. Inadequate sleep unable to express clearly the nature swinging, or regular sessions of jumping can certainly contribute to behavioral or source and intensity of the pain, or bouncing, and applying deep pressure, problems and should be considered prior behavioral changes may result. For

Autism Spectrum Disorder: Parents’ Medication Guide 7 instance, headaches may cause otherwise unexplained emotional new interactions or awareness that head banging or hitting. Dental changes or severe emotional shifts. highlight the family’s strengths and problems may go unnoticed if the successes. At the same time, family child will not allow examination of Family Interventions therapy changes the interactions among family members that may accidentally his or her teeth. Bodily injuries can Although raising a child with ASD can encourage unwanted behaviors. result from a high level of activity be fulfilling and rewarding, it can also and a low pain threshold. be an overwhelming experience that The most researched parent can negatively impact the health and interventions are those that help parents • Gastrointestinal discomfort may well-being of parents and families. to manage the child’s behavior (e.g. be caused by constipation or Interventions intended to provide parent management training (PMT)) and diarrhea, acid reflux, food allergies, support and education for families those that enhance skill-based therapies or inflammatory bowel . of children with ASD can provide (e.g. parent ABA training). Although Constipation is by far the most reduction to reduce tension in less researched than PMT or ABA, there common gastrointestinal problem in the home environment, which in turn are also treatments that foster parent- children with ASD and should always may positively impact the behavioral child emotional connections in order be considered as a possible source functioning of the child.8 to improve communication, skills, and of problems. emotional balance. Families should be Comprehensive treatment should attend encouraged to talk with other families • Seizures are more prevalent in to the well-being and functioning of the and their providers about different children with ASD than in the general entire family. Parent and sibling support treatment options. They should also population. Symptoms of seizures groups can help family members feel consider the first meeting with a new can include staring spells, involuntary less alone. Supportive therapy for therapist as an evaluation in which they movements, confusion, or headaches. parents or families can address the learn what can be offered and whether Less common features are sleep challenge of raising a child with special there is a good fit between the family’s changes, behavioral problems, or needs. Family therapy aims to create difficulties and the therapist’s skills.

8 Autism Spectrum Disorder: Parents’ Medication Guide Medication as a Treatment Tool for Emotional or Behavioral Challenges

n addition to the interventions outlined in and family physicians often see many children the previous chapter, medication is another with ASD, and many times can appropriately I tool that may play a role in the treatment of recommend a medication for symptoms. Others the child with ASD. It is important to recognize, with more specialized training include child and however, that the medications currently used adolescent psychiatrists, child neurologists, and to treat symptoms and behaviors associated developmental-behavioral pediatricians. Parents with ASD have not at this point in time been should feel free to ask doctors about their level shown to improve the core features of autism. of training and experience with patients with In other words, there is no medication to treat ASD, and if they feel comfortable prescribing the autism itself. medication, or if they prefer to seek consultation from more specialized or experienced providers. Medication may be recommended to reduce symptoms of an emotional or behavioral disorder Important Factors to Consider for in a child with ASD. These co-occurring disorders are more common than once thought, and Medication Treatment include ADHD, anxiety, and , among • Informed consent. A clear and thorough others. The symptoms and findings that discussion between the parent or guardian and to these diagnoses are the same as those for the prescriber should explain the diagnosis, children without ASD, but may require a provider symptoms, non-medication treatment options, with experience in ASD to recognize them. and expected duration of treatment. For the child or adolescent taking medication, Armed with this knowledge, it may be easier the provider can obtain his/her permission to understand some of the reasons for use by offering information about why they are of medication in children with ASD. Use of taking medication and the symptoms that medication in ASD is common, but the number the medication is meant to treat. These of children with ASD that are prescribed discussions should take place not just at medications has also raised concerns among the beginning of medication treatment, These co-occurring 9 some doctors and parents. A study in 2013 but be ongoing, so that as issues arise and disorders are more reported that nearly two out of three children symptoms change, treatment can be modified with ASD had been prescribed a psychoactive to meet the child’s needs. common than once medication during the three-year study period, thought, and include and one in seven children had been treated with • Risks and expected benefits. Risks include three or more medications at the same time. the known side effects from the product label ADHD, anxiety and (if studied in children and adolescents), adult Appropriate use of medication requires an use side effects (may have different side depression, ongoing trusting relationship between parents effects than in youth), published research, and among others. and providers, and clear information about when the experience of the treating clinician with to use and not use medication for symptoms in the medication. Expected benefits would be to children with ASD. When parents have questions reduce the target symptoms. If the medication about medication use in their children, they is effective in reducing target symptoms, should seek the advice of a professional with other benefits may arise, including improved training in ASD. Board certified pediatricians functioning in school, with peers, and at home.

Autism Spectrum Disorder: Parents’ Medication Guide 9 • Which medication will work? Medication • Adequate dose and length of trials are exactly that—trials. Prescribers medication trial. It is important to speak do not have good enough information with your child’s provider about how to predict which medication will be the long to stay on a medication. Some best option for each individual child. A medications may take effect sooner medication trial is a time-limited period than others. For example, of testing a medication for the individual medications like may child. Most clinicians start at a low dose take effect very quickly compared to to minimize side effects and increase selective serotonin reuptake inhibitors slowly to a target dose based on the (SSRIs) like citalopram, , or child’s age, weight, and his/her response. , which may take several weeks Once on the target or maximum to take effect. While it can be difficult to tolerated dose, for many medications, predict the duration of treatment needed, the prescriber will then wait four to addressing this topic can be informative eight weeks for the full benefit to take and build an understanding between effect. If a child does not benefit after prescriber and family. that time period, it is time to reassess • Understanding effects. In the situation, taper off the ineffective general, prescribers, families whose child medication, and consider starting the is being treated with a medication, and child on an alternate medication. often the patients themselves would like medications to be helpful and have • Level of evidence supporting the use of a positive response. This is a natural a particular medication for a particular reaction. It is important to understand problem. When considering which that even in large, well designed drug medication to use for a particular set of studies where families and prescribers symptoms, clinicians and families can do not know if the child is receiving refer to several sources of information an active drug or a placebo (inactive about effectiveness, including the table sugar pill), one in three or four of those provided at the end of this guide. Two receiving placebo will report significant medications are approved by the Food treatment-associated improvement. and Drug Administration (FDA) to treat Clearly, this placebo effect can make it irritability in autism: and more difficult to understand if a drug . Other medications may have is truly providing clinical benefit. Given been originally studied in youth or adults this fact, it is important to try to be as without autism. objective as possible when assessing the impact of a drug on your child. • Understanding “off-label” uses of Sometimes it can be helpful to receive medication. When the FDA approves a input from others who know your medication, it allows a pharmaceutical There are numerous child, such as teachers, therapists, or company to advertise that medication for other family members. Families will off-label medications a specific purpose. When a medication is sometimes ask if they should inform not FDA-approved for a particular clinical that physicians use to treat school administrators or teachers about purpose, it is termed “off-label.” There a medication change. This common problems associated with are numerous off-label medications question is designed to increase the that physicians use to treat problems ASD. The provider should strength of objective or unbiased associated with ASD. The provider assessment. Depending on the drug explain to a parent or should explain to a parent or guardian and the need to have others observe whether or not a medication is off-label. guardian whether or not the child for adverse effects, this option This does not mean the medication can be considered. Some providers may a medication is should not be prescribed to the child ask the parent or caregiver or teacher to off-label. with ASD. The decision to use a certain complete standardized rating scales to medication should be based on available measure changes. research, but when research is limited, it may be based on evidence from studies • When to stop a medication. First, it is on children or adults without ASD and generally a good idea to discuss stopping clinical judgment. a medication with the prescriber before

10 Autism Spectrum Disorder: Parents’ Medication Guide doing so. This is important because some What if medications fail? ASD is a complex of alternative therapies (with the exception medications may require lowering the disorder that can be difficult to treat. If a of for sleep), many of these dose in gradual steps to avoid potential medication fails, it is time to reassess the popular remedies, such as diet or vitamins, withdrawal effects. It is also important problem and see if an alternate explanation, are relatively harmless. It should be noted, to have an open dialogue with your therapy, or medication may be helpful. If however, that any treatment always requires prescriber about what criteria will be used the child’s symptoms do not improve after effort and expense, consuming resources to determine success and when to stop multiple medications and other treatment that could be used for more evidence-based a medication. Prior to starting a new drug trials, other options may be considered, treatments. There are some treatments, it is important for families to understand particularly if severe aggressive and/or self- however, that parents should not consider. injurious behaviors pose a threat to the child what symptoms and/or behaviors the These treatments not only do not work and or others. prescriber is hoping to alleviate with the are expensive, but may pose serious health medication. Families can take an individual There are approximately 10 specialized risks to the child. approach to defining “success” in response • child psychiatry hospital units in the to the medication, and discuss this with Chelation removes toxic metals from U.S. These specialized psychiatric • the prescriber at the time the medication is the blood and is used to treat cases units for children and adolescents with started and at follow-up visits. of severe lead poisoning and elevated developmental typically use iron associated with particular blood There can be many reasons for stopping a multi-modal approach that combines disorders. Scientific tests of chelation as a medication: the medication may have medication and behavioral treatment with a treatment for ASD have not shown it to adverse effects on the child, the child’s communication and be effective and the procedure can have symptoms may not respond to the strategies. Although waiting lists for these units may be long, there is preliminary dangerous side effects, including kidney medication, or the child’s family may not evidence that such an intensive approach and liver failure, cardiac arrest, and has be able to pay for the medication. Stopping can be helpful.10 There are also many even resulted in the deaths of at least a medication is a personal decision best day treatment, specialized school, and two children with autism. made in consultation with the prescriber. residential treatment programs that focus Hyperbaric oxygen treatment (HBOT) is • Combining medication treatment on children with developmental disabilities • the administration of oxygen to a patient with other forms of treatment. We and emotional and behavioral challenges. in a pressurized chamber, and is used know that combining medication for While evidence for the effectiveness of behavioral issues with interventions such these programs is generally not available, for a handful of conditions, including as occupational, speech, physical, and programs that use evidence-based decompression sickness and different behavioral therapies may provide the best practices, such as applied behavioral types of soft tissue damage. There is a lack chance for some patients and families analysis (ABA), and that take a multi- of scientific evidence for using this costly to achieve the best outcomes. It would disciplinary approach are more likely to procedure in children with autism, which be rare to find that use of a medication be beneficial. can cause lung, vision, and sinus damage, completely replaces the need for other as well as rupture of the middle ear. • Electroconvulsive therapy (ECT) In rare types of therapies. In many instances, instances, ECT can be considered in is the most studied medication effective medication use may maximize • the treatment of patients who have very in children with autism, and has the benefits patients with ASD receive severe aggressive and/or self-injurious repeatedly been shown in multiple from other types of therapy. behaviors that do not respond to other scientific studies to have no effect. Side interventions and are driven by a co- It is important to share information effects can include diarrhea, vomiting, • existing psychiatric condition, such as about the use of all natural remedies fever and blood clots. a or (a state and/or alternative treatments with your of muscle rigidity and stupor or great child’s clinician. Certain supplements and • Stem cell re-implantation is a excitability). While there is no controlled alternative treatments can interact with potentially promising therapy for many evidence, several case studies have prescription medicines. For instance, St. diseases. However, experts have reported ECT to be helpful in a few such John’s Wort, which some people take as a cautioned that the field is at least a individuals, though common side effects natural treatment to alleviate depression decade away from the development of ECT include headache and nausea, symptoms, may have a negative of effective treatments. There is no and short-term memory loss during the scientific evidence for the use of interaction with prescribed selective initial course of treatment. serotonin reuptake inhibitor (SSRI) drugs. stem cell procedures in autism, costs Given this fact, it is imperative to provide Are there treatments that should not can exceed six figures, and injecting a complete list of supplements and other be used? Approximately three-quarters dead or deteriorating stem cells into a alternative treatments your child may be of children with autism have been given person can cause potentially fatal side receiving to his or her treating clinician to alternative treatments. Although there is effects, including stroke and increase safety and effectiveness. little evidence supporting the vast majority brain inflammation.

Autism Spectrum Disorder: Parents’ Medication Guide 11 Symptoms and Medications

edications can be used to target a disorders. Haloperidol (Haldol), another anti- wide range of specific symptoms psychotic, also has evidence of benefit for M in children and adolescents with irritability and aggression, suggesting that this ASD, some of which are listed below. A table general class of medications may be helpful summarizing the controlled research evidence in children with ASD. Little evidence supports for medications in children with autism is other types of medications; although the side located at the end of this guide. effects associated with can lead parents and physicians to try medications • Irritability, tantrums, and aggression: that have single controlled studies to support Irritability, tantrums and aggression are their use, including or common reasons for families to seek (Tenex or Intuniv). treatment for their child with ASD. Children who are irritable are prone to become upset or • Self-injurious behavior (SIB) can be a angry easily, sometimes leading to tantrums, significant and distressing problem for children property destruction, or aggression. Irritability and their families. Almost 11% of children with can range from mild, where the only noticeable ASD in a community survey were stated to problem is that a child cries more easily than have SIB, including hitting, biting, or scratching peers when frustrated; to severe, where a child directed at themselves.11 SIB can range from may be so prone to aggression that they need mild to very severe. Some children will engage to be hospitalized. Addressing symptoms in a mild self-injurious behavior, such as lightly when a child is young may prevent them hitting their chin, but may do it so often that Clinicians should from worsening as a child gets older and over time they eventually produce an injury. physically larger. Clinicians should evaluate Other children may only occasionally engage evaluate the potential the potential contributing factors to irritability in self-injury, such as banging their head on an contributing factors and aggression in a particular child before object, but may do it with such force, that even prescribing medication, as detailed in the a single episode could cause serious injury. Self- to irritability and assessment section of this guide. injury that is part of a suicidal episode (such as aggression in a cutting one’s wrists) is less common in children Medication can be considered to reduce with ASD, though some higher-functioning particular child before irritability and aggression when contributing individuals may engage in suicidal actions. factors do not appear to explain the symptoms prescribing medication, or these contributing factors have been The best evidence for effective treatment of as detailed in the addressed without resolving the problem. SIB is with applied behavioral analysis (ABA). assessment section Two anti-psychotic medications, risperidone In this method, the provider performs an (Risperdal) and aripiprazole (Abilify) have been analysis to try to determine the source of the of this guide. shown to reduce tantrums and aggression SIB, which is typically escaping from demands, in multiple large controlled studies in accessing preferred items or activities, children with ASD, but each of them can also attention-seeking, or changing sensory lead to significant side effects, including input or pain.12 Functional communication increased appetite and weight gain, changes strategies have also been shown to reduce in cholesterol, sedation, and movement problem behaviors in ASD, including self-

12 Autism Spectrum Disorder: Parents’ Medication Guide injury.13 Medication may play a role in forms), has been shown to be effective successful in improving repetitive symptoms addressing SIB, particularly if the SIB is for ADHD in children without ASD, and of obsessive compulsive disorder (OCD) determined to be related to other mental may be helpful if methylphenidate is in children without ASD, clinicians have health problems, such as anxiety or ineffective.18 (Strattera) has attempted to treat repetitive behaviors in depression. also been researched in controlled studies ASD with SSRIs. However, controlled studies for treatment of ADHD in children with of SSRIs—including fluoxetine, , The atypical anti-psychotics, risperidone and autism, and showed some improvements, and citalopram—have shown little or no aripiprazole, have been studied for treatment particularly for hyperactivity and benefit in improving repetitive behaviors of irritability in children with ASD, which can impulsivity,19, 36 and common side effects in ASD.23–25 The atypical antipsychotics, 14,15 include self-injury. were nausea and vomiting, decreased risperidone and aripiprazole, have shown appetite, and drowsiness. Guanfacine limited evidence of reducing repetitive Inattention, hyperactivity, and impulsivity, • (Intuniv, Tenex) has also shown benefit in behavior in children with ASD. the cluster of symptoms referred to as a large study of children with ADHD and attention deficit-hyperactivity disorder ASD.20 In small single studies of children with There are a number of other areas that (ADHD), are common in children with autism, naltrexone21 and clonidine22 showed can be a focus of clinical concern in ASD and can be a treatable source of possible benefit for children with ADHD. children with ASD, and practitioners and challenges. Most recent surveys have families may consider medication, though identified ADHD symptoms in 30–60% • Repetitive behavior and insistence there is little or no controlled evidence for 16 of children with autism. While reduced on sameness: In their play activities effectiveness. These areas include anxiety interest and attention to the social and daily routines, children with ASD and depression, inappropriate sexualized environment is a typical feature of ASD, may display repetitive behaviors behavior, , , , significant inability to focus on tasks, and insistence on sameness. These , and social communication. or high levels of motor activity that are behaviors can manifest as: present across different settings, such as • Anxiety or depression can occur Repeated motor mannerisms (such school and home, are not typical of ASD • in children with ASD, and cognitive as hand flapping) alone and could indicate the presence of behavioral therapy has been shown to be co-occurring ADHD. • Atypical sensory interests helpful for high functioning children with (manifested as touching or rubbing ASD and anxiety. While no medication There are a number of reasons a child could certain textures) has been directly studied for anxiety or be very hyperactive, impulsive, or inattentive depression in ASD, most practitioners Complex body movements across settings besides ADHD. Hyperactivity • will consider the use of a SSRI, such as or impulsivity may occur in younger children • Repeating a sound, word, or phrase fluoxetine or sertraline, both of which who do not have enough structure in their many times have strong evidence for reducing anxiety day, or do not have a functional means of Interruption of these repetitive patterns and depression in children without communication. Inattention may occur or the daily environments of children ASD. As part of assessing anxiety, the in children who are highly anxious and with autism may cause anxiety or even possibility of post-traumatic stress distracted by their worries or are overly aggression due to their insistence on should be considered. sensitive to stimuli in the environment. In sameness and inflexible adherence to Inappropriate sexualized behavior these cases, structuring the environment, specific routines. • providing visual and positive behavior (ISB): When a person does not follow supports, and addressing anxiety may It is important to note that repetitive behaviors recognized social , socially reduce ADHD-like symptoms. As always, a vary greatly among children with autism, unacceptable behaviors often occur, and careful consideration of why the child may in both types and frequency of behaviors, sometimes this includes disinhibited be hyperactive, impulsive, or inattentive and while some individuals only engage in or inappropriate sexualized behavior should precede treatment. repetitive behaviors when feeling anxious, (ISB). Adolescents with ASD are often others may do so constantly. Therefore, discouraged from expressing their For children with inattention, hyperactivity, when considering medication treatment, sexuality and many are deprived of or impulsivity that do not respond it is essential to determine whether these adequate sexual education. It is also to environmental and/or behavioral behavioral patterns are a problem or not. important to note that people with approaches, methylphenidate (Ritalin Repetitive behaviors can be unobtrusive or developmental disabilities are particularly and similar forms) has been shown to even adaptive (for example, obsessing about vulnerable to , and ISB can be a 26 be effective in approximately half of model airplanes and developing a passionate possible indicator of child sexual abuse. 17 children with autism and ADHD. Appetite interest in learning how to build them), or To treat ISB, most clinicians recommend suppression is common, and headaches, can be interruptive and cause difficulties for starting with educational or behavioral 27 insomnia, or irritability can occur. While it academic and social functioning. approaches. There are case reports has not been specifically tested in children describing use of mirtazapine (Remeron) with autism, a similar type of medication, Because selective serotonin reuptake to treat ISB in adolescents with ASD, salts ( and similar inhibitor (SSRI) medications have been though there is no controlled evidence.28–30

Autism Spectrum Disorder: Parents’ Medication Guide 13 Medications such as • Psychosis (the loss of reality-based, Author Disclosures (SSRIs) or antipsychotics may organized thinking) can occur rarely decrease libido, which could be helpful, in children with ASD. CRAIG ERICKSON, MD though this is untested.31,32 Leuprolide medications that have evidence of Associate Professor, UC Department was described in one case report to benefit in children without ASD are of reduce ISB in a young adult male with typically used in these cases. Cincinnati Children’s Hospital ASD,33 but has potential side effects of Research Funding: The Roche Group, depression, seizures, and anaphylaxis, Resource links: Cincinnati Children’s Hospital, the John as well as ethical considerations. • AACAP practice parameter Merck Fund, Autism Speaks, Angelman http://www.jaacap.com/article/ Insomnia (sleep problems) appears Foundation, American Academy • S0890-8567%2813%2900819-8/pdf to be prevalent in children with of Child and Adolescent Psychiatry (AACAP), Simons Foundation, SynapDx ASD and should be first addressed • Autism speaks by removing electronics and other https://www.autismspeaks.org/ Advisor/Consultant: Confluence stimulating activities from the Pharmaceuticals, the Roche Group, Alcobra bedroom, developing a consistent CDC website http://www.cdc.gov/ • Books, Intellectual Property: Indiana bedtime routine, and addressing bed- ncbddd/autism/index.html University, Cincinnati Children’s Hospital wetting if needed. For children who continue to have trouble falling or • Others Other: Confluence Pharmaceuticals staying asleep, melatonin has been • ChildTrends http://www.childtrends. (equity interest) shown in a number of controlled org/?indicators= studies to improve sleep in some autism-spectrum-disorders JEAN A. FRAZIER, MD Vice Chair of the Division of Child and children with ASD. NIMH http://www.nimh.nih.gov/ • Adolescent Psychiatry health/publications/a-parents- Social communication is a core • guide-to-autism-spectrum- University of Massachusetts deficit area in ASD and a number disorder/index.shtml Medical School of psychosocial treatments have Research Funding: Alcobra, Janssen been developed to address this area. ATN tool kits https://www. • Research and Development, Pfizer, Inc., Medication is limited to the possible autismspeaks.org/family-services/ Neuren, Roche, Seaside Therapeutics, use of methylphenidate, which was tool-kits shown in one study to potentially SyneuRx International, National Institute improve social communication, • Autism Speaks challenging behaviors of Mental Health (NIMH), National perhaps by increasing attention toolkit https://www.autismspeaks.org/ Institute of Neurobiological Disorders and and focus. family-services/tool-kits/ Stroke (NINDS) challenging-behaviors-tool-kit Other: Forest Pharmaceuticals—data • Pica is the eating of non-nutritive safety Monitoring Board for an adolescent substances and can have serious depression study medical consequences. Although historically attributed to nutritional TONIA FERGUSON deficiencies, many people with pica Vice President, External Affairs do not have demonstrable vitamin Autism Society of America or mineral deficits, though they are typically evaluated. Nevertheless, iron ERIC GOEPFERT, MD deficiency is the most common cause Director, Child and Adolescent of pica, and pica behaviors usually Consultation Liaison Service; Child and disappear once the deficiency is Adolescent Psychiatrist corrected.34 Applied behavior analysis Tufts Medical Center (ABA) continues to have the strongest evidence for treatment of pica. No Disclosures

• Bruxism is the repetitive clenching and grinding of teeth, often occurs during sleep, and appears to be more frequent in patients with developmental delays, including ASD.35 To date, behavioral interventions remain the mainstay of treatment.

14 Autism Spectrum Disorder: Parents’ Medication Guide QUENTIN A. HUMBERD, MD, FAAP ADELAIDE ROBB, MD MATTHEW SIEGEL, MD Director at Child and Family Behavioral Associate Professor, Psychiatry Director, Developmental Disorders Health System and Pediatrics Program, Maine Behavioral Healthcare Blanchfield Army Community Hospital Children’s National Medical Center Associate Professor of Psychiatry Advisor/Consultant: Vanderbilt Kennedy Leadership Roles: Chief of and Pediatrics, Tufts University Center Treatment and Research Institute Divisions, Children’s School of Medicine for Autism Spectrum Disorders (TRIAD) National Health System Faculty Scientist II Maine Medical Center Research Institute GAGAN JOSHI, MD Research Funding: American Academy of Director, Autism Spectrum Disorder Child and Adolescent Psychiatry (AACAP), Research Funding: NIMH, Simons Program in Pediatric Psychopharmacology Actavis/Forest, Lundbeck, National Center Foundation, Nancy Lurie Marks for Advancing Translational Sciences Family Foundation Medical Director, the Alan and (NCATS), National Institute of Neurological Lorraine Bressler Program for Autism Disorders and Stroke (NINDS), Pfizer, Inc., JEREMY VEENSTRA-VANDERWEELE, MD Spectrum Disorder SyneuRx, Sunovion Pharmaceuticals, Mortimer D. Sackler Associate Professor, Massachusetts General Hospital Supernus Pharmaceuticals Research Psychiatrist for Children Advisor/Consultant: Actavis/Forest, Columbia University Research Funding: Forest Research Cambridge University Tech Serv (CUTS), Leadership Roles: Psychopharmacology Laboratories, Duke University, Schering- Ironshore Pharmaceuticals, Lundbeck, Committee/Working Group—Co-chair, Plough Corporation, Shire Inc., ElMindA, National Institute of Child Health and Autism Speaks Autism Treatment Network, Pamlab, LLC, U.S. Department of Defense Human Development (NICHD), Pfizer Inc., Vanderbilt University Department of Rhodes, Tris Pharmaceuticals Psychiatry—Division Director of Child and LOUIS KRAUS, MD Speakers Bureau: Actavis/Forest, Pfizer, Adolescent Psychiatry Chief, Section of Child and Inc., Takeda Pharmaceuticals Adolescent Psychiatry Research Funding: Roche, , Books, Intellectual Property: Guilford Press SynapDx, Seaside Therapeutics, Forest Woman’s Board Professor of Child Psychiatry In-kind Services: AACAP, American Advisor Consultant: Roche, Academy of Pediatrics (AAP), American Novartis, SynapDx Rush University Medical Center College of Osteopathic Pediatricians Other: Springer (editorial stipend), Other: American Psychiatric Association (ACOP), Actavis/Forest, American Wiley (editorial stipend) (Chair of Council on Children, Adolescents, Professional Society of ADHD and Related and Family), American Medical Disorders (APSARD), Bracket, Lundbeck, PAUL WANG, MD Association (member of Council of Pfizer, Inc., Rhodes, Society for Maternal- Senior Vice President Science and Public Health) Fetal Medicine, Sunovion Pharmaceuticals, Autism Speaks Supernus Pharmaceuticals, Takeda, Tris AMY LUTZ, MA, MFA Pharmaceuticals Leadership Roles: Autism Speaks— President full time employee and Honorarium/Other: AACAP, AAP, ACOP, Senior Vice President EASI Foundation: Ending Aggression and Actavis/Forest, Bracket, Eli Lilly (stock Self-Injury in the Developmentally Disabled in IRA), Glaxo Smith Kline (stock in IRA), CAROL COHEN WEITZMAN, MD Books, Intellectual Property: Author—Each Johnson and Johnson (stock in IRA), Professor of Pediatrics, Director, Day I Like It Better: Autism, ECT, and the Neuronetics (DSMB Chair), NIMH (DSMB Developmental-Behavioral Pediatrics Treatment of Our Most Impaired Children Chair), Pfizer, Inc. (stock in IRA), Society for Program; Director, Yale Adoption/Foster Maternal-Fetal Medicine, Sentara Hospital Clinic; Fellowship Program Director, ALICE MAO, MD Developmental Behavioral Pediatrics Professor, Psychiatry and Family: William Gaillard, MD (spouse)— Behavioral Sciences Treasurer of the American Society Yale University Baylor College of Medicine Leadership Roles: American Academy of Pediatrics—Executive Committee of Associate Medical Director Section of Developmental Behavioral DePelchin Children’s Center Pediatrics, Society for Developmental Behavioral Pediatrics—Program Chair Advisor/Consultant: Shire Inc. Speakers Bureau: Sunovion Pharmaceuticals, Arbor, Roche Pharmaceuticals, Otsuka America Pharmaceutical, Takeda Pharmaceuticals USA, Inc.

Autism Spectrum Disorder: Parents’ Medication Guide 15 Major Depressive yo) (≥8 Disorder yo) OCD (≥7 Psychosis Tourette’s Disorder B • • B yo) OCD (≥10 B • • yo) (both ≥3 FDA Approval Status Approval FDA in autism, A=Approved in youth B=Approved

Seizures (N=2) Seizures Seizure (4%; N=1) (13%) Lethargy (6%) Tremors (3%) Tachycardia Insomnia (3%) (3%) Diaphoresis Nausea/ (3%) vomiting (3%) Anorexia Serious SEs Serious None 12% (N=9) on study medication terminated AEs: due to treatment • • 38% (N=12) on study medication terminated AEs: due to treatment • • • • • • • None None likely on likely

less Insomnia (38%) (38%) energy Increased Diarrhea (26%) (19%) Nausea/Vomiting Impulsivity (19%) (12%) Hyperactivity (11%) (7%) Insomnia (29%) Constipation (25%) Sedation (25%) (21%) Twitching (17%) Tremor (17%) Flushing Dry mouth (13%) Decreased appetite (13%) Sedation (78%) Irritability (28%) EPS (>25%) Sedation EPS Side effects Associated with Study Medication Associated Side effects (SEs) Effects Side None were (AEs than placebo) fluoxetine 97% on study medication AEs: experienced • • • • • • • • • • • • • • • • NR • • • • • Irritability Hyperactivity Withdrawal Relatedness Hyperactivity tantrums Temper Withdrawal Stereotypies Relatedness Hyperactivity tantrums Temper Treatment Treatment Response symptom Target YES NO (Irritability) YES • • NO YES • • • • • YES • • • • • Range)

Dose (mg/day) Dose Mean Dose (Dose 10mg ±4 (2.5–20) [once a day] 16.5mg ±6.5 (2.5–20) [once a day] 152mg ±56 25–250 [in 2 divided doses a day] 128mg (100–150) [in 2 or 3 divided a day] doses 1mg (0.5–3) [in 2 divided doses a day] 0.8 ±0.6mg (0.25–4) [in 2 divided doses a day] CONTROLLED MEDICATION STUDIES IN ASD IN STUDIES MEDICATION CONTROLLED Study Duration Short-term (8-week) Short-term (12-week) Short-term (10-week) Short-term (7-week) Short-term (14-week) [4-week on study medication] Short-term (14-week) [4-week on study medication] Participants RangeAge (years) Youth (5–16) Youth (5–17) Youth (6–18) + Adults Youth (10–36) [10–18] Youth =27/36 Children (2–6) Children (2–7) Controlled Trial Controlled in ASD et al.,Hollander 2005 King et al., 2009 et al.,Gordon 1993 et al.,Remington 2001 et al.,Anderson 1984 et al.,Anderson 1989 Medication Generic Name Name) (Trade Inhibitor Reuptake Serotonin Fluoxetine (Prozac) Citalopram (Celexa) Clomipramine (Anafranil) Agents Antipsychotic Typical Haloperidol (Haldol) Target Symptom(s) Repetitive behaviors Repetitive behaviors Repetitive behaviors Autism ASD

16 Autism Spectrum Disorder: Parents’ Medication Guide

Schizophrenia yo) (≥13 yo) (≥10 Schizophrenia yo) (≥13 Bipolar Disorder yo) (≥10 Tourette’s Disorder yo) (6–18 B • • B • • • FDA Approval Status Approval FDA in autism, A=Approved in youth B=Approved A Irritability yo) (5–17 A Irritability yo) (6–17 Constipation (N=1) Sedation (N=7) (N=4) (N=4) Tremor Fatigue Vomiting gain Weight SIB Agitation Serious SEs Serious None None • 10% on study medication terminated treatment AEs: due to • • • 11% on study medication terminated treatment AEs: due to • • • • •

Increased appetite (73%) Increased (59%) Fatigue Sedation (49%) (27%) Drooling Dizziness (16%) gain Weight Somnolence (73%) EPS (28%) appetite (23%) Increased (13%) Headache Constipation (13%) gain (10%) Weight appetite (6%) Increased (2%) Drowsiness gain (2%) Weight Sedation (24%) (15%) Fatigue (13%) Vomiting appetite (12%) Increased (10%) Tremors (9%) Drooling EPS (7%) gain (4%)Weight gain (29%) Weight (21%) Fatigue Somnolence (17%) (15%) Vomiting EPS (15%) appetite (15%) Increased Sedation (11%) (9%) Drooling Diarrhea (9%) (9%) Pyrexia Side effects Associated with Study Medication Associated Side effects (SEs) Effects Side • • • • • • participantsAll (100%) on study medication AEs: experienced • • • • • • • • • 88% on study medication AEs: experienced • • • • • • • • • • • • • • • • • •

Hyperactivity Stereotypies Repetitive behaviors Anxiety Hyperactivity Inappropriate speech Social withdrawal Stereotypies Repetitive behaviors Stereotypies reaction Affectual Sensory response Socialization Communication Daily living skills Hyperactivity Stereotypies Inappropriate speech Repetitive behaviors Hyperactivity Inappropriate speech Stereotypies Repetitive behaviors Treatment Treatment Response symptom Target YES • • • YES • • • • • YES • • • • behaviors: Adaptive • • • YES • • higher dose At (15 mg/day): • • YES • • • • Range)

Dose (mg/day) Dose Mean Dose (Dose 1.8 ±0.7mg (0.5–3.5) [in 2 divided doses a day] 1.2mg [once a day] 2.1 ±0.8mg 4.5) (up to 5–15mg 8.5mg (2–15) CONTROLLED MEDICATION STUDIES IN ASD IN STUDIES MEDICATION CONTROLLED Study Duration Short-term (8-week) Short-term (8-week) Long-term (6-month) Short-term (8-week) Short-term (8-week) Participants RangeAge (years) Youth (5–17) Children (5–12) Youth (6–17) Youth (6–17) Controlled Trial Controlled in ASD 2002 RUPP, Shea et al., 2004 2005 RUPP, Williams et al., 2006 et al.,Marcus 2009 et al., 2009 Owen Medication Generic Name Name) (Trade Agents Antipsychotic Atypical Risperidone (Risperdal) Trial Continuation RUPP Open-label Aripiprazole (Abilify) Target Symptom(s) Irritability** Irritability**

Autism Spectrum Disorder: Parents’ Medication Guide 17 Schizophrenia Bipolar Disorder B • • (both ≥13 yo) B yo) (≥6 ADHD B yo) (≥6 ADHD B yo) (≥6 ADHD FDA Approval Status Approval FDA in autism, A=Approved in youth B=Approved Aggression (2%) Aggression gain (2%) Weight ideation (N=1) Suicidal Irritability (8%) Dysphoria (N=1) Tiredness (N=1) Rage outburst with violence and (N=1) hospitalization (N=1) Fatigue Serious SEs Serious 11% on study medication terminated treatment AEs: due to • • • None 18% on study medication terminated treatment AEs: due to • 1 participant discontinued study AE medication due to • • • •

Decrease in BP (33%) Decrease gain (23%) Weight (19%) Vomiting EPS (15%) appetite (13%) Increased (12%) Pyrexia URI (12%) Insomnia 10%) Sedation (67%) gain (67%) Weight appetite (50%) Increased Constipation (50%) appetite (18%) Decreased Insomnia (15%) Irritability (10%) Emotional outbursts (10%) Increased (21%) stereotypy (21%) Upset stomach Sleep difficulties (14%) Emotional lability (7%) Mood swings/irritability (44%) appetite (38%) Decreased (31%) Upset stomach (31%) Nausea/vomiting (31%) Tiredness/fatigue Racing heart (19%) Insomnia (19%) (13%) Headache Rash (13%) Restlessness (13%) Constipation (6%) Diarrhea (6%) Dry mouth (6%) (29%) Nausea/vomiting appetite (27%) Decreased (23%) Fatigue Early morning (10%) awakening Side effects Associated with Study Medication Associated Side effects (SEs) Effects Side 87% on study medication experienced AEs: • • • • • • • • • • • • • • • • 50% on study medication AEs: experienced • • • • • • • • • • • • • • • • • 81% on study medication experienced AEs: • • • • Hyperactivity Inappropriate speech Stereotypies Repetitive behaviors Treatment Treatment Response symptom Target YES • • • • YES (in global functioning) YES YES YES YES YES Range)

Dose (mg/day) Dose Mean Dose (Dose 10mg (1–15) 10 ±2mg (7.5–12.5) 7.5–50mg [in 3 divided doses a day] 14 ± 4mg (5–20) [in 2 divided doses a day] 1.4mg/kg/day 2(divided into of total a day; doses 20–100mg) 20–100mg (1.2 mg/kg/day) [in 2 divided doses a day] CONTROLLED MEDICATION STUDIES IN ASD IN STUDIES MEDICATION CONTROLLED Study Duration Long-term (52-week) Short-term (8-week) Short-term (4-week) Long-term (8-week) Short-term (1+2-week) Short-term (6-week) Short-term (8-week) Participants RangeAge (years) Children (6–14) Children (5–14) Pre-schoolers (3–6) Children (5–15) Youth (6–17) Controlled Trial Controlled in ASD et al.,Marcus 2011a et al.,Marcus 2011b et al.,Hollander 2006 2005 RUPP, Ghuman et al., 2009 et al., 2006 Arnold, Harfterkamp et al., 2013 Medication Generic Name Name) (Trade (Zyprexa) Agents Anti-ADHD Methylphenidate (Ritalin) Atomoxetine (Strattera) Atomoxetine (Strattera) Target Symptom(s) ASD Hyperactivity/ Impulsivity ADHD ADHD

18 Autism Spectrum Disorder: Parents’ Medication Guide B yo) (6–17 ADHD B (6–17 yo) ADHD B yo) (6–17 ADHD B Disorder Seizure yo) (≥10 B Disorder Seizure yo) (≥2 B Disorder Seizure yo) (≥1 FDA Approval Status Approval FDA in autism, A=Approved in youth B=Approved

Verbal and physical Verbal requiring aggression police contact and ER visit (N=1) Irritability & insomnia (N=1) Insomnia (N=2) Insomnia+ (N=1) Aggression (N=1) Stereotypy Serious SEs Serious None • None None • • • • None None Drowsiness (50%) Drowsiness (14%) (86.7%) Drowsiness (63.3%) Fatigue (43.3%) appetite Decreased Emotional/tearful (40%) Dry mouth (40%) Irritability (36.7%) (30%) Anxiety (38%) Drowsiness (25%) Hypotension activity Decreased Irritability (33%) gain (22%) Weight (11%) Aggression (11%) Anxiety (13%) Agitation (13%) Skin rash (13%) gain (6%) Weight Insomnia Hyperactivity (30%) Agitation/Aggression Side effects Associated with Study Medication Associated Side effects (SEs) Effects Side • • • • • • • • • • • • 77% on study medication side effects: experienced • • • • • • • • • • • None Irritability Hyperactivity Social withdrawal Inappropriate speech Treatment Treatment Response symptom Target YES YES NO • YES YES NO NO YES (and Parent-rated not Clinician-rated) in: improvement • • •

Range)

Dose (mg/day) Dose Mean Dose (Dose 2.8mg (2–3) [in 3 divided doses a day] 1–4mg/day 0.15–0.20mg (4–10 micro-gm/ kg/day) [in 3 divided doses a day] 823 ± 326mg (500–1500) ≥500 mean serum(dosed to of 90 mg/mL) level [in 2 divided doses a day] 60–200mg (5 mg/kg/day) 863 ±279 mg(350– 2500) 20–30 mg/kg/day NR CONTROLLED MEDICATION STUDIES IN ASD IN STUDIES MEDICATION CONTROLLED Study Duration Short-term (4-week) Short-term (8-week) Short-term (6-week) Short-term (8-week) Short-term (12-week) Short-term (18-week) [12-week on study drug] Short-term (10-week) Short-term (Duration NR) Participants RangeAge (years) Children (5–8) Children (5–14) Children (5–13) Youth (5–17) Included participants with ID Youth (4–15) Majority Children (3–11) NR Children (5–10) Majority Children (7.4 ± 3.2) Majority Controlled Trial Controlled in ASD et al.,Handen 2008 Scahill et al., 2015 Jaselskis et al., 1992 et al.,Hollander 2005 et al.,Hollander 2010 et al., 2001 Belsito et al., Wasserman 2006 et al., Niederhofer 2002 Medication Generic Name Name) (Trade Guanfacine (Tenex) Guanfacine (Intuniv) Clonidine (Catapres) Mood Stabilizers / Divalproex sodium (Depakote) Lamotrigine (Lamictal) Levetiracetam (Keppra) Agents Cholinergic Galantamine (Razadyne) Target Symptom(s) ADHD ADHD ADHD symptoms Repetitive behaviors Irritability/ Aggression Autism ASD Irritability

Autism Spectrum Disorder: Parents’ Medication Guide 19 B yo) (≥1 Flu FDA Approval Status Approval FDA in autism, A=Approved in youth B=Approved Irritability (N=4) Diarrhea (N=2) Irritability (N=1) (N=1) Enuresis (N=1) Hypokalemia Serious SEs Serious • • None None • • • 1 participant discontinued study AE medication due to None Irritability (22%) Diarrhea (11%) Constipation 50% Insomnia (21%) Somnolence (11%) (43%) Nausea/vomiting Constipation (21%) Diarrhea (21%) (22%) Hypokalemia Irritability discomfortStomach Side effects Associated with Study Medication Associated Side effects (SEs) Effects Side • • • 74% on study medication AEs: experienced • • • • • • • • None Hyperactivity Inappropriate speech Stereotypies Social motivation Treatment Treatment Response symptom Target NO to (Refer comments) NO NO (and Clinician-rated not parent-rated) in: improvement • • YES • • • YES YES YES Range)

Dose (mg/day) Dose Mean Dose (Dose 1.25–2.5mg 0.5–5mg 168mg (90–200) [in 2 [5 mg/kg/day] divided doses a day] 900-2700mg (900 mg once, twice, foror thrice a day 4-week each) 1mg 50 mg/kg/day 3mg (Controlled-release formulation) CONTROLLED MEDICATION STUDIES IN ASD IN STUDIES MEDICATION CONTROLLED Study Duration Short-term (6-week) Short-term (14-week) Short-term (4-week) Short-term (12-week) Short-term (12-week) Short-term (12-week) Short-term (12-week) Participants RangeAge (years) Children (2–10) NR Children (4–12) Youth (5–15) Children (3–10) Children (3–11) Children (3–10) Children (4–10) Controlled Trial Controlled in ASD Chez et al., 2003 et al., 2012 Arnold King et al., 2001 et al.,Hardan 2012 Lemonnier et al., 2012 Geier et al., 2011 Cortesi et al., 2012 Medication Generic Name Name) (Trade Donepezil (Aricept) Mecamylamine (Inversine) Modulating AgentsGlutamate Amantadine (Symmetrel) N- (Mucomyst, Acetadote) Agents GABAergic (Bumex) AgentsMiscellaneous L-Carnitine (Carnitor) Melatonin Behaviors under irritability include aggression, deliberate self-injury, and temper tantrums; NR=Not reported; AEs=Adverse effects; OCD=obsessive compulsive disorder; EPS=Extra-pyramidal symptoms; SIB=Self injurious symptoms; EPS=Extra-pyramidal disorder; compulsive OCD=obsessive tantrums; NR=Not reported; and temper effects; AEs=Adverse self-injury, deliberate under irritability include aggression, Behaviors behaviors; URI=Upper respiratory tract ; LDL=Low-density lipoprotein; HDL= High- density lipoprotein; TG=Triglycerides; MPH=Methylphenidate; TG=Triglycerides; density lipoprotein; High- HDL= LDL=Low-density lipoprotein; infection; tract URI=Upper respiratory behaviors; Intellectual =IQ<70; Target Symptom(s) Core Symptoms Core Symptoms Irritability + Hyperactivity Irritability Core Symptoms Core Symptoms Insomnia *  ** 

20 Autism Spectrum Disorder: Parents’ Medication Guide Medication Tracking Form

Use this form to track your child’s medication history. Bring this form to appointments with your provider and update changes in medications, doses, side effects and results.

Date Medication Dose Side Effects Reason for keeping/stopping

Autism Spectrum Disorder: Parents’ Medication Guide 21 References

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