Bob Klaehn, M.D. Bob Klaehn, M.D. October 3, /30/14

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1 Bob Klaehn, M.D. October 3, Bob Klaehn, M.D. Medical Director, Arizona Division of Developmental Disabilities since 2001 Faculty, MIHS Child Psychiatry Residency Program Child Psychiatrist, District Medical Group Board Member, Infant and Toddler Mental Health Coalition of Arizona Mental Health Advisory Board, Child Welfare League of America Member of AACAP s Committee on Systems of Care since 1995 Clinical Interests: Autism and Intellectual Disability Wraparound Services Treatment of Medically Ill Children with Psychiatric Disorders Infant Psychiatry 2 1

2 What are Evidence-Based Practices? A treatment or service that has been studied, usually in an academic or community setting, and has been shown to be effective, in repeated studies and conducted by several investigative teams. From: Choosing the Right Treatment: What Families Need to Know about Evidence-Based Practices (2007) National Alliance for the Mentally Ill (NAMI) 3 Availability of evidenced based practice Many evidenced-based practices are only available in a limited number of communities across the country. Many mental health providers have not been trained in evidence-based practices. 4 2

3 Evidence-Based Practice and Co-occurring Disorders Many studies that support evidencebased practices are NOT do not include children with co-occurring disorders. When there are co-occurring disorders, such as Autism and anxiety, for example, families may request information on several different interventions that may be helpful. 5 How to Talk with Providers about Treatment Choices and Evidence-based Practices Why are your recommending this treatment and what are the alternative treatments? What is the goal of the treatment being recommended and will it help us get the outcomes we want? How will we know if we are reaching our treatment goals? 6 3

4 How to Talk with Providers about Treatment Choices and Evidence-based Practices (2) How does the recommended treatment promote my child s strengths, capabilities and interests? What are the risks and benefits associated with the recommended treatment? How does the recommended treatment work? 7 How to Talk with Providers about Treatment Choices and Evidence-based Practices (3) Is there research or evidence to support the use of this treatment? What training and experience do you have in the recommended treatment? If you are not recommending an evidence-based practice, why not? 8 4

5 How to Talk with Providers about Treatment Choices and Evidence-based Practices (4) How will our family be involved in the recommended treatment and how can we best support the treatment? What changes can we expect to see and how long will it take before we see these changes? How do we measure and monitor progress? 9 How to Talk with Providers about Treatment Choices and Evidence-based Practices (5) What should we do if problems get worse or we do not see an improvement? How do we get help after hours? If we can t reach you, who is covering for you? Is the recommended treatment covered by our insurance and what is the cost? 10 5

6 Questions for Psychiatric Medication Providers about Evidence-Based Practices Are there psychosocial interventions that might be tried before medication is used, or effectively used in combination with medication (which may help to lower the dose of the needed medication)? Does research support the use of the recommended treatment for a child that is my child s age and with similar needs? 11 Questions for Psychiatric Medication Providers about Evidence-Based Practices (2) How does the medication fit within the overall treatment plan and how will we coordinated with other treatments, such as therapy (individual, group or family) or school behavior plans? What changes in behavior or symptoms should we be looking for? 12 6

7 Questions for Psychiatric Providers about Evidence-Based Practices (3) What are the potential risks, benefits and side effects from this medication? How will our family, our child and the other treating providers to monitor progress, behavior changes, symptoms and safety concerns? 13 Questions for Psychiatric Providers about Evidence-Based Practices (4) How will we know when it is time to talk about stopping medication treatment and what steps need to be taken before the medication is stopped? What if my child has a crisis and is hospitalized? (Make sure that the hospital doctor and your community psychiatric medication provider communicate!!) 14 7

8 Evidenced Based Psychosocial Interventions Bringing the Family, Child, Provider and/or Teacher Together Cognitive Behavior Therapy (CBT) Exposure Therapy for Anxiety Behavior Therapy in its various forms, including: Positive Behavior Support Early Intensive Applied Behavioral Analysis Interpersonal Therapy 15 Evidenced Based Family Interventions Brief Strategic Family Therapy Functional Family Therapy Parent Management Training Family Education and Support 16 8

9 Evidence Base for Combined Treatment with Medication and Therapy Treatment of Depression with CBT and Selective Serotonin Reuptake Inhibitors (SSRIs) Treatment of Depression with CBT and Selective Serotonin Reuptake Inhibitors (SSRIs) Treatment of Autism with Parent Management Training and Risperidal (Risperidone) more on this later. 17 Behavioral Treatment and Normal Educational and Intellectual Functioning in Young Autistic Children Ivor Lovaas original study of Early Intensive Applied Behavioral Analysis (EIABA) was completed at UCLA and was published in 1987 Research Hypothesis: Construction of a special, intense and comprehensive learning environment for very young autistic children would allow some of them to catch up with their normal peers by first grade. 18 9

10 Lovaas (1987) 19 children were in the experimental group and received more than 40 hours of one-to-one treatment per week. 40 children were in the control group and were treated with 10 hours or less of on-to-one treatment. Mean age at beginning participation in the study: 34.6 months old Pre-treatment measures revealed no significant differences between the intensively treated group and the minimally treated control groups. 19 Lovaas (1987): Results 47% achieved normal intellectual and education functioning with normalrange IQ scores and successful first grade performance in public schools 40% were mildly retarded and assigned to special classes for the language delayed 10% were profoundly retarded and assigned to classes for the autistic/ retarded Treatment group 2% achieved normal intellectual and education functioning 45% were mildly retarded and assigned to special classes for the language delayed 53% were severely retarded and placed in autistic/retarded classes Control group 20 10

11 Lovaas: From the discussion The treatment schedule of subjects who achieved normal functioning could be reduced from 40 hours per week to infrequent visits even after the first two years of treatment. The assignment of one full-time special education teacher for two years would cost an estimated $40,000 in contrast to the nearly $2 million incurred (in direct costs alone) by each client requiring lifelong institutionalization. 21 The Importance of Replication of Research Studies Why is replication important? Because it confirms the previous result It increases the number of persons who have been studied (statistical measures are stronger with larger numbers) Helps to establish the medical necessity of a device, procedure or treatment Replications of Lovaas original study of EIABA: Smith et al (2000) Howard et al (2005) Sallows and Graupner (2005) Cohen et al (2006) Remington (2007) 22 11

12 Sallows and Graupner (2005) Intensive Behavioral Treatment for Children with Autism: Four-Year Outcome and Predictors Twenty-four children with autism were randomly assigned to a clinic-directed group, replicating the parameters of the early intensive behavioral treatment developed at UCLA, or to a parentdirected group that received intensive hours but less supervision by equally well-trained supervisors. 23 Sallows and Graupner (2005) Age at intake into study: between 24 and 42 months Outcome after 4 years of treatment, including cognitive, language, adaptive, social and academic measures, was similar for both groups. 48% of all children showed rapid learning, achieved average post-treatment scores, and at age 7, were succeeding in regular education classrooms

13 Sallows and Graupner (2005) Treatment outcome was best predicted by the pre-treatment presence of: Imitation: Social skill acquisition was also predicted by the pretreatment ability to imitate. Language Social responsiveness Average Full Scale IQ for all 23 children increased from 51 to 76, a 25 point increase 25 Sallows and Graupner (2005) The number of weekly hours of treatment seemed less related to outcome than pretreatment variables. Consistent with previous studies, low IQ (below 44) and the absence of language (no words at 35 months) predicted limited progress

14 Sallows and Graupner (2005): Parent Involvement Parent directed children, who received 6 hours per month of supervision did about as well as clinic directed children, although they received much less supervision. Ratings of parental involvement were weakly related to outcome, suggested that more over efforts to increase parent s feeling capable of contributing to treatment planning may enhance treatment effects. 27 Cohen et all (2006) Early Intensive Behavioral Treatment: Replication of the UCLA Model in a Community Setting 3 year study compared 2 groups: 21 children who received hours per week of Early Intensive Behavioral Treatment from a community agency 21 age- and IQ-matched children in special education classes at local public schools All children in the study were under 48 months at treatment onset

15 Cohen et all (2006) Conclusions The present study suggests that the UCLA/Lovaas Model of early intensive behavioral treatment can be implemented in a non-university community-based setting. the non-significant group x time interactions in the statistical analyses indicates that the EIBT group did not show reliable IQ increases relative to the comparison group after Year 1. A possible explanation is that most gains occurred in the first year of the intervention. 29 Remington (2007) Early Intensive Behavioral Intervention: Outcomes for Children with Autism and their Parents after Two Years. An intervention group (n = 23) of preschool children with autism were identified on the basis of parent preference for early intensive behavioral interaction and a comparison group (n = 21) identified as receiving treatment as usual. All children were months when they entered the study

16 Remington (2007) All children in the intervention group received home based early intensive behavioral intervention for 2 years. Groups did not differ on assessments at baseline but after 2 years, robust difference favoring intensive behavioral intervention were observed on measures of intelligence, language, daily living skills, positive social behavior and a statistical measure of best outcome for individual children. 31 Remington (2007) His study found that the intervention showed robust group main effects after 24 months of intervention were found for: Measurements of both Expressive Language and Language Comprehension IQ Mental Age Vineland Daily Living Skills 32 16

17 Why is EIABA medically necessary? Because it is not experimental under AHCCCS guidelines Lovaas original study has been replicated at least 5 times with the same results, with a total of 258 children studied Experimental is defined as: Services that are associated with treatment or diagnostic evaluation and that are not generally and widely accepted as a standard of care in the practice of medicine in the United States unless: the weight of the evidence in peer-reviewed articles in medical journals published in the United States supports the safety and effectiveness of the service; or In the absence of peer-reviewed articles, for services that are rarely used, novel, or relatively unknown in the general professional medical community, the weight of opinions from specialists who provide the service attests to the safety and effectiveness of the service. 33 Why is EIABA experimental for children over age four? Only Eikeseth et al: Outcome for Children with Autism Who Began Intensive Behavioral Treatment Between Ages 4 and 7, (2007) shows that EIABA can be effective for children aged children in the treatment group, 12 children in the control group (25 total) This study has not been replicated 34 17

18 Eikeseth et al (2007) Children in this study began treatment at a mean age of 5.5 years old When participants enter school (the year they turned 6 years old), their weekly treatment hours were reduced from a mean of 28 to a mean of 18 hours. Conclusion: In a follow-up of the same group of children at a mean age of 8 years, 2 months, the behaviorally treated children showed larger increases in scores with intervention than did the eclectic treatment group and less severe aberrant behavior and fewer social problems at follow-up. 35 Eikeseth et al (2007) Conclusions Most gains in IQ and communication appeared between intake and Year 1. In contrast, Vineland Composite scores increased throughout ABA treatment and significant changes in Vineland Socialization and Daily Living scores occurred only after 1 year of ABA treatment. This finding suggests that it may be important to extend ABA treatment beyond 1 year to achieve reliable gains in social behavioral and daily living skills

19 Eikeseth et al (2007) Eikeseth and his colleagues concluded that more study is needed to determine the effectiveness of Intensive ABA for this age group: Because the identification of the age range during which intensive ABA is most effective has important ramifications for public policy, further research to resolve the conflicting findings is warranted. 37 Duration of Hab- M Treatment Initial Authorization: 2 years (150 hours of HBM Supervision) Should the data show that the child is continuing to benefit from the intervention, 2 additional six month periods of intervention may be approved, one at a time Revised Autism Guidelines call for data collection using the Vineland Adaptive Behavior Scales at intake, 1 year of treatment and 1 year, 9 months of treatment to obtain this data

20 Research support for duration of treatment Howlin, Magiati and Charman (2009) looked at Lovaas and its replications and found: Average duration of treatment was 2.7 years Children with better language skills benefited more Children with higher IQ scores benefited more 39 Howlin, Magiati and Charman also stated: In Remington et al s (2007) study, there is a mean increase in IQ of 8 points in the first year and a further increase of 4 points in the subsequent year. Although these increases are not negligible, they do suggest that the main impact of intervention is in the first year and, thereafter, increases, at least in IQ, tend to plateau in those 3 studies that also showed changes in Vineland Adaptive Behavior Scale (VABS) scores over several time points, the diminution after the first year was even more marked

21 Research evidence supports Parental Participation Sallows and Graupner (2005) and Remington (2007) indicate that the results of ABA interventions are enhanced by parent participation. 41 What is the Evidence Base for a Comprehensive ABA Program for Older Children and Adolescents? Outlined in the 2009 article by Granpeesheh et. al., Applied behavior analytic interventions for children with autism: A description and review of treatment research The Journal of Family Practice Online

22 Granpeesheh et. al. Hundreds of studies have been published in peer-reviewed journals on the ABA for older children. The scope and duration of research studies on ABA for older children with ASD are significantly narrower and shorter that those of EIBI. : 43 Granpeesheh et. al. Whereas the goal of long-term EIBI studies has been to remediate all skill deficits displayed by participants, the goal of most research on ABA for older children with Autism has been to identify ad remediate particular deficits in a short period of time

23 Granpeesheh et. al. For example, goals of ABA research for older children might include teaching one particular skill of independent living, or reducing one particular challenging behavior by replacing it with functional communication. 45 Granpeesheh et. al. Therefore, most of the studies [described in this article] address a small number of behaviors for a short period of time (e.g.1 or 2 months). As such, these studies address individual components of what might be considered a comprehensive program 46 23

24 Potential Clinical Focuses for Intervention Language: Research has demonstrated that the basic components of ABA intervention can be combined and used to improve language of children of all ages. Types of language which have bee intervened upon run the gamut of human communication, from simple non-vocal requesting visa picture exchange and naming of familiar objects via sign language 47 Potential Clinical Focuses for Intervention (2) Academics: ABA procedures have bee used to teach a variety of academic and pre-academic skills to individuals with ASD. Once a child becomes school age, the acquisition of academic skills become the responsibility of the school system

25 Potential Clinical Focuses for Intervention (3) Social Functioning: Research has demonstrated ABA procedures to be effective I treating the full range of social skills. 49 Potential Clinical Focuses for Intervention (4) Challenging Behaviors: Research has indicated that ABA procedures have been particularly successful in assessing and treating challenging behaviors in persons with ASD. The general approach [is] to identify why a challenging behavior occurs and to teach the individual an alternative, appropriate means to communicate to have their needs met. Such an approach is referred to as functional communication training and has bee the subject of a substantial amount of treatment research

26 Potential Clinical Focuses for Intervention (5) Independent Living Skills: ABA procedures have bee applied to teaching older children and adolescents with ASD a variety of independent living skills, for example how to seek assistance when lost. 51 Potential Clinical Focuses for Intervention (6) Vocational Skills: ABA procedures have been used to assess and establish vocational skills in individuals with ASD. Feeding Disorders: A significant amount of research has demonstrated the effectiveness of ABA procedures for treating pediatric feeding disorders in persons with developmental disabilities

27 Granpeesheh: A Consultative Model Just as the scope and duration of research studies o ABA for older children with ASD are narrower and shorter term than those of EIBI research, service provision programs may often have a narrower focus and emphasize higher- priority short term goals. 53 Granpeesheh: A Consultative Model (2) Such programs often function on a consultative model, wherein the day-today care providers for older children with ASD contact an ABA provider for help when they are at a loss as to how to solve particular problems

28 Now let s review the evidence base for selected medication interventions in Autism ADHD Use of Selective Serotonin Reuptake Inhibitors (SSRIs) Epilepsy in Autism Use of Risperdal (Risperidone) Use of Risperdal (Risperidone) with Parent Training Use of more than one antipsychotic at a time 55 RUPP Autism Network Study of Ritalin (Methylphenidate - MPH) in Children with PDD + Hyperactivity 72 children (ages 5-14) with Autism, Asperger s or PDD, NOS and significant ADHD symptoms. Study design: 7 day trial dose period 4 week double blind trial of three dose levels (0.125, 0.25 and 0.50 mg/kg/dose of MPH TID and a placebo in random order 56 28

29 Stimulants: Ritalin (Methylphenidate MPH) & Dexedrine (Dextroamphetamine - DA) Owley, The Pharmacological Treatment of Autistic Spectrum Disorders CNS Spectrums 2002; 7(9):663-9 Despite being used at a high rate and the well documented efficacy of stimulants in treating children with ADHD, the response rate in Autism Spectrum Disorders may be lower and side effects may be higher. 57 RUPP Autism Network Study of Ritalin (Methylphenidate - MPH) in Children with PDD + Hyperactivity (2) 6 out of 72 subjects were unable to tolerate the dosage increases and were dropped from the study. Only 58 of the remaining actually finished the study, most of the rest dropping out due to side effects. Irritability was the most common reason for intolerability

30 RUPP Autism Network Study of Ritalin (Methylphenidate - MPH) in Children with PDD + Hyperactivity (2) 44 subjects were rated as responders to at least 1 week of treatment (35 in MPH group and 9 in placebo group) Subject age, IQ and weight did not moderate treatment response. Subjects with Asperger s Disorder and PDD, NOS were more likely to be classified as responders to both MPH and placebo than persons with Autism. 59 RUPP Autism Network Study of MPH in Children with PDD + Hyperactivity Summary 35/72 (49%) of subjects responded to MPH 13/72 (18%) exposed to MPH dropped out of study due to adverse effects 60 30

31 RUPP Autism Network Study of MPH in Children with PDD + Hyperactivity Summary 35/72 (49%) of subjects responded to MPH 13/72 (18%) exposed to MPH dropped out of study due to adverse effects 61 Algorithm for treating hyperactivity and/or inattention in PDD Stigler, Posey & McDougle Step 1: Start with Behavioral Therapy Step 2: Continue BT; obtain baseline EKG and add alpha 2 adrenergic agonist (AAA) Step 3: Discontinue AAA: start low-dose stimulant (Ritalin or Adderall) Step 4: Discontinue stimulant and start atypical antipsychotic; obtain baseline liver function, fasting lipid and glucose values Current Psychiatry Vol. 3. No. 7 July 2004, pp

32 Review of the Research using of Selective Serotonin Re-Uptake Inhibitors (SSRIs) for the Core Symptoms of Autism Lead author of review, Katrina Williams, Ph.D., stated: It s not surprising that clinicians and parents have hoped that SSRIs will help core features of autism as well as associated problems, but there is no strong evidence they do. Review looked at seven studies looking at four SSRIs: Prozac (Fluoxetine), Luvox (Fluoxamine), Pondimin (Fenfluramine) and Celexa (Citralopram) Cochrane Database Syst Rev. (2010), 8 63 Review of the Research using of Selective Serotonin Re-Uptake Inhibitors (SSRIs) for the Core Symptoms of Autism In the seven studies, there were 271 participants Limited evidence for benefit in adults only: 2 studies (total of 36 participants) Improvement in clinical global impression with Prozac & Luvox Improvement in OCD behaviors with Luvox Improvement in anxiety with Prozac Improvement in aggression with Luvox However, there are no studies of treatment of conditions cooccurring with Autism, such as Obsessive Compulsive Disorder (OCD) or depression with: Zoloft (Sertraline) Paxil (Paroxetine) Lexapro (Escitalopram) 64 32

33 Epilepsy in Autism Studies indicate that 15-30% of children with Autism will have seizures An additional 10-25% will have abnormal EEGs without clinical seizures Incidence of Seizures is dependent on the etiology of Autism. For example, children with tuberous sclerosis and certain genetic syndromes have a higher incidence of seizures 65 Anticonvulsants (1) Owley: Because 25-33% of persons with autism have seizures, the psychopharmacolgical management of persons with autism must take epilepsy and the potential role of anticonvulsants into consideration. Clinical experience: The better the seizure control, the better the behavior

34 Anticonvulsants (2) Hollander et al, An open trial of divalproex sodium in autism spectrum disorders J Clin Psychiatry 2001;62 (7): subjects, ages 5-40 were given a mean dose of 768 mg/d and mean blood level of 75.8 mcg/ ml. Affective instability, repetitive behavior, impulsivity and aggression improved in 10 Adverse reactions: sedation, weight gain, hair loss, behavioral activation and elevated liver enzymes 67 Anticonvulsants (3) Studies in non-autistic populations have shown effectiveness of these medications in reducing aggressive behavior and treating bipolar disorder. Cycling mood disorders can occur in persons with Autism and should be treated appropriately

35 Anticonvulsants (4) Depakote (Valproic Acid) for irritability with Prozac in children with Autism Double-blind, placebo controlled trial in 13 male children with autism Irritability scores remained stable in the group pretreated with Depakote Prozac initiated at 10mg QOD then titrated up or down for therapeutic effect. Initiation with very low doses is less likely associated with early activation J Clin Psychopharmacol 2006; 26: Atypical Antipsychotics: RUPP Study of Risperdal (Risperidone) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network, Risperidone in children with autism and serious behavioral problems. Double-blind, placebo controlled study of 101 children and adolescents, with a mean dose of 1.8mg per day. After 8 weeks, 69% of the Risperidone group responded, in contrast to 12% of the placebo group N Engl J Med 2002; 347(5):

36 Atypical Antipsychotics: RUPP Study of Risperdal (2) Risperidone found effective in reducing aggression, agitation, hyperactivity and repetitive behavior. Side effects include weight gain (mean 2.7kg), increased appetite, sedation, dizziness and hypersalivation. 71 RUPP Risperidone/Parent Management Training Trial 124 children (4 to 13 years) with Pervasive Developmental Disorders and significant irritability 24 week, three site, randomized, parallel groups trial Children randomized 3:2 to Combined (COMB) treatment (n=75) or Medication only (MED) treatment (n=49) Aman, McDougle, et. al. Medication and Parent Training in Children with Pervasive Developmental Disorders and Serious Behavior Problems: Results from a Randomized Clinical Trial JAACAP (December 2009) 72 36

37 RUPP Risperidone/Parent Management Training Trial (2) Instruction included use of preventative approaches, such as: Use of visual schedules Effective use of positive reinforcement Teaching compliance Teaching functional communication skills Teaching functional adaptive skills 73 RUPP Risperidone/Parent Management Training Trial (3) On the Home Situations Questionnaire: COMB > MED (P =.006 COMB > MED on Aberrant Behavior Checklist: Irritability (P =.01) Stereotypic Behavior (P =.04) Hyperactivity/Non-compliance (P =.04) Final Risperidone dose: MED = 2.26 mg/day COMB = 1.98 mg/day (P =.04) 74 37

38 FDA Approved Atypical Antipsychotics now approved for treatment of Autism RISPERDAL (Risperidone) is used for the treatment of irritability associated with autistic disorder in children and adolescents ages 5-16 years. (Risperdal.com) ABILIFY is indicated for the treatment of irritability associated with autistic disorder in pediatric patients (ages 6 to 17), as part of a total treatment plan. (Abilify.com) 75 What does FDA Approval Mean? It means that drug company that made the medication can advertise that its product is effective. Off-label prescribing means that the medication is being used for a non-fda approved purpose. Medication prescribed off-label may have an evidence base

39 As DDD Medical Director I often review the behavioral health records of persons with Developmental Disabilities being treated for severe behavioral problems. In these reviews, I have found: Many individuals are being treated with two neuroleptics Most of these individuals are still having significant behavioral problems despite this treatment. 77 When do you use two neuroleptics? A Survey of Presenters at the Advanced Psychopharmacology Update at 2009 AACAP Meeting Christopher McDougle (Indiana University): A small number (5%?) may need combined treatment to control aggressive behavior in youth with Autism. Christoph Cornell (Albert Einstein): Only combination shown to have benefit is Aripiprazole and Clozapine, but he cautioned that this is experimental. Harold Carlson (Stony Brook University): Adding Aripiprazole to another neuroleptic to block prolactin in an individual with symptomatic hyperprolactinemia 78 39

40 Relative Risk for Developing Metabolic Syndrome on Atypicals (H. Carlson, 2009) Current research suggest the following ranking for the antipsychotic medications: Clozaril (Clozapine) = Zyprexa (Olanzapine) > Risperdal (Risperidone) = Serquel (Quietapine) > Abilify (Aripiprazole) = Geodon (Ziprasidone) Relative risk for diabetes and hyperlipidemia follow the same order Taking Depakote or Lithium with these medications may increase the risk of weight gain. 79 Summary Little or no evidence to support the use of two atypical antipsychotics All atypical antipsychotic medications are associated with some weight gain

41 Thank you very much! Questions? Discussion? 81 41