Autism: Overview, Treatment, and Communication

Transcription

1 Autism: Overview, Treatment, and Communication MALAURA CREAGER, PHARMD NMPHA SPRING 2019

2 Disclosures No conflicts to disclose

3 Learning Objectives Pharmacists and technicians: Describe the criteria used to diagnose autism Identify common comorbidities for autism Evaluate the effectiveness of their communication with a person with autism Pharmacists: Recommend and monitor pharmacological treatment for autism and its comorbidities

4 Autism and Pharmacists Pharmacy school may not cover the disorder Not enough specialists psychiatrists Primary care managing patients Higher frequency of adverse effects Patients and caregivers frustrations with their providers Incredible time commitment and confusion

5 Outline Diagnosis criteria Epidemiology Etiology Pathophysiology Pharmacotherapy Communicating with autism patients and their families

6 Autism Spectrum Disorder (ASD) Developmental disorder characterized by social, communication, and behavioral challenges Signs often noticed early in life but diagnosis can be delayed Generally life-long disorder Formerly known as Autistic syndrome Asperger disorder Pervasive developmental disorder not otherwise specified Diagnostic and Statistical Manual of Mental Disorders, 5 th Ed. APA, 2013

7 Diagnosis

8 Diagnosing No laboratory tests Evaluate behavior and history Trained professionals can diagnose by age 2 Symptoms often noticed younger Understanding the definition is important for the healthcare team Diagnosis includes 4 required sections Deficits in social communication interactions Restricted, repetitive behavior, interests, or activities Present in early development, but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life Cause clinically significant impairment in functioning Diagnostic and Statistical Manual of Mental Disorders, 5 th Ed. APA, 2013

9 Diagnosis part 1: Deficits in Social Communication Interactions 3 out of 3 required deficits Social-emotional reciprocity Non-verbal communication Developing, maintaining, and understanding relationships What this looks like: #nofilter Taking turns in conversations Not understanding unspoken messages Not understanding layered levels of relationships Perspective-taking Peer pressure Diagnostic and Statistical Manual of Mental Disorders, 5 th Ed. APA, 2013

10 Diagnosis part 2: Restricted, repetitive behavior, interests, or activities 2 out of 4 required for diagnosis Stereotyped or repetitive motor movements, use of objects, speech Insistence on sameness/ritualized behavior Restricted, fixated interests Hypo-hyperreactive to sensory input What this looks like: #nofilter Difficulty with transitions Stimming Lining up toys Single topic of conversation Great with routines, and patterns Sensory overload & meltdowns Diagnostic and Statistical Manual of Mental Disorders, 5 th Ed. APA, 2013

11 Diagnosis parts 3 and 4 Part 3 Present in early development, but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life Part 4 Cause clinically significant impairment in functioning Diagnostic and Statistical Manual of Mental Disorders, 5 th Ed. APA, 2013

12 Diagnosis: Severity for parts 1 and 2 Level 1 Requiring support Level 2 Requiring substantial support Level 3 Requiring very substantial support Diagnostic and Statistical Manual of Mental Disorders, 5 th Ed. APA, 2013

13 Severity vs Spectrum

14 Severity vs Spectrum: The patient s perspective

15 Severity vs Spectrum: The patient s perspective

16 Epidemiology WHO IS MOST AFFECTED

17 Child Prevalence 8-year-old children 325,483 8% total population

18 Child Prevalence

19 PREVALENCE PER 1,000 CHILDREN ADDM Prevalence over time Baio J et al. MMWR Surveill Summ. 2018; 67(SS-6): 1-23

20 ADDM key findings Gender Ratio Intellectual Ability

21 and 30% had not been recognized by their community provider by age 8

22 Adult prevalence Fewer studies Estimated similar to children Adults more likely to have severe disabilities For those no longer autistic, high rates of comorbidities Lord C et al. Lancet published online

23 Pharmacist prevalence? Bernard J. Crespi. Front Neurosci. 2016;10:300

24 Comorbidities* Medical Seizures Gastrointestinal issues Malnutrition Obesity Constipation Asthma Allergies Bone fractures Pneumonia Down s syndrome Psychiatric *But are they really Sleep disorders Irritability (communication) Hyperactivity Anxiety Depression Obsessive-compulsive disorder Lord C et al. Lancet published online Jones KB et al. Autism. 2016; 20(5) Buck TR et al. J Autism Dev Disord. 2014; 44(12):

25 Clinical issues Gender identity Transition to adulthood Suicide risk Patient vs caregiver goals Blood draws for anything Time burden/commitment Insurance coverage Access to services Cassidy S et al. Lancet Psychiatry. 2014; 1(2): Heylens G et al. J Autism Dev Disord. 2018; 48: 2117 Nicolaidis C et al. Autism 2015; 19(7):

26 Neurodiversity Autism is part of the normal diversity of human brains Humanity has benefited from contributions of people with autism Many communicate very well, especially in writing Frustration with a lack of voice in their care Neurodiversity movement may be biased toward high-functioning, average IQ Typical presentation Drowns out voices of low functioning patients and families who need more care Nicolaidis C et al. Autism 2015; 19(7): Lord C et al. Lancet published online

27 Etiology

28 Risk factors Maternal environment Nutrition Medication Valproic acid Opioids prior to conception Pesticides Parental age Birth circumstances Low birthweight Preterm birth MMR vaccine No Lord C et al. Lancet epub ahead of print Rubenstein E et al. J Autism Dev Disord epub ahead of print

29 Genetics Identified genetic causes Not clearly identified Fragile X Heritability 70-93% Older sibling with autism 7%-20% of subsequent siblings Lord C et al. Lancet epub ahead of print

30 Pathophysiology #NOFILTER

31 Neurobiology Brain volume Overgrowth early in development Altered connectivity Overall under-connectivity Over-connectivity in specific regions (especially frontal and occipital lobe) Reduced/impaired growth later in development GABA signaling/switch Lord C et al. Lancet epub ahead of print Ben-Ari Y. Trends in Neurosciences. 2017;40(9), Courchesne E et al. Brain Res. 2010;1380: Zielinski BA et al. Brain. 2014; 137 (6); Lobe Frontal Occipital Parietal Temporal Cerebellum Brainstem Normal function Personality, behavior, emotions Judgment, planning, problem solving Speech: movement and writing (Broca s area) Body movement (motor strip) Intelligence: concentration, self-awareness Vision (Color, light, movement) Interprets language, words Sense of touch, pain, temperature Interprets vision, hearing, motor, memory Spatial and visual perception Understanding language (Wernicke s area) Memory Hearing Sequencing and organization Balance, coordination, posture Autonomic functions: breathing, heart rate, temperature, wake and sleep cycles, digestion, sneezing, coughing, vomiting, swallowing

32 Treatment

33 Guideline recommendations Screening No recommendation from US Preventative Services Task Force Recommended by most other authorities Prevention Folic acid Vitamin D Treatment Largely parent training or therapy interventions Coaching parents and caregivers on how to interact with children with autism School-based interventions Equine or guinea pig therapy No first line drug therapy May use medications for comorbidities if necessary

34 Choosing medication treatment Know what the actual diagnosis is Define the goals of therapy Use a validated tool to measure the progress toward goal Use evidence, but be aware of the limitations of evidence in this population Be suspicious of adverse reactions, including paradoxical Goel R, Hong JS, Findling RL, Ji NY. An update on pharmacotherapy of autism spectrum disorder in children and adolescents. Int Rev Psychiatry Feb;30(1): doi: /

35 Treatment overview Irritability and aggression Stereotypy ADHD Depression/ anxiety Sleep disorders Core symptoms? Risperidone Methylphenidate Atomoxetine Children: Few studies Melatonin Bumetanide Folinic acid Aripiprazole Haloperidol * Clonidine* Buspirone* Valproate* Guanfacine* Naltrexone* Adults: possibly SSRIs Awareness of transitions Olanzapine* Vitamin D3* Goel R et al. Int Rev Psychiatry. 2018; 30(1); Lord C et al. Lancet epub ahead of print * = single study or mixed evidence

36 Treatment: Irritability and aggression RISPERIDONE ARIPIPRAZOLE

37 Treatment: Irritability and aggression Risperidone and aripiprazole FDA approval: irritability associated with autistic disorder in pediatric patients For tantrums, self-injurious or violent behavior Reserve for those who are at risk for serious adverse events Best for stabilization label indicates to increase dose to therapeutic effect, then titrate downward to reduce adverse events Head to head trial: neither superior to the other

38 Dosing Titration Ages Initial Recommended Maximum Dose Schedule Aripiprazole mg/day 5-10 mg/day 15 mg/day 5mg/day 1 week Risperidone <20kg 0.25 mg/day 0.5 mg/day 3 mg/day 0.25 mg/day Initial: 4 days Risperidone 20kg mg/day 1 mg/day 3 mg/day 0.5 mg/day Subsequent: 2 weeks

39 Aripiprazole & Risperidone Prolactin levels Risperidone increased Aripiprazole decreased May dose either once daily, but twice daily may decrease somnolence Side effects: weight gain, somnolence, anticholinergic, vomiting, constipation, EPS (not akathisia) Lowers seizure threshold Check for dose adjustments for CYP3A4 and CYP2D6 drug interactions and genetic tests Fluoxetine, paroxetine, carbamazepine Possible Risk of TdP These drugs can cause QT prolongation BUT currently lack evidence for a risk of TdP when taken as recommended.

40 Treatment: Core symptoms FOLINIC ACID BUMETANIDE

41 Bumetanide TREATMENT for core symptoms

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43 Adult neurons Fetal neurons Gamma aminobutyric acid (GABA) Allows chloride to enter the cell Normal action Chief inhibitory neurotransmitter Normally chloride level within cell is low Hyperpolarizes cell = inhibits action potential Fetal neurons Chloride levels high GABA is a stimulatory neurotransmitter

44 Paradoxical effects: Benzos and barbiturates in some epilepsy Lord KT et al. Jasper s Basic Mechanisms of the Epilepsies. 4 th edition.

45 Paradoxical effects: Benzos and barbiturates in some epilepsy Lord KT et al. Jasper s Basic Mechanisms of the Epilepsies. 4 th edition.

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48 Bumetanide in autism 2017 Prospective, randomized, controlled N=88; 2-18 years Duration: 3 months Intervention: Bumetanide 2 mg BID: n=22 Bumetanide 1 mg BID, n=23 Bumetanide 0.5 mg BID, n=23 Placebo, n=23 Outcomes: Childhood Autism Rating Scale (CARS), Clinical Global Impressions Scale (CGI), Social Responsiveness Scale (SRS)

49 Bumetanide 2017 results

50 Bumetanide 2017 Potassium

51 Treatments: Other conditions Depression/anxiety SSRIs have not been studied in children, but poorly tolerated Adults: SSRIs better tolerated Sleep disturbances Melatonin ADHD/hyperactivity Methylphenidate Atomoxetine Epilepsy Dietary issues: constipation Overall: Use guideline recommendations Monitor closely for adverse effects Goel R et al. Int Rev Psychiatry. 2018; 30(1); Lord C et al. Lancet epub ahead of print

52 Treatments: Mixed, poor, or lacking evidence N-acetylcysteine Memantine Donepezil SSRIs for core symptoms Lamotrigine Levetiracetam Clomipramine Arbaclofen Lithium Oxcarbazepine Topiramate Oxytocin Digestive enzymes Sulforaphane Omega-3 fatty acids Goel R et al. Int Rev Psychiatry. 2018; 30(1); Lord C et al. Lancet epub ahead of print

53 Communication

54 Communication Pharmacist-autism communication struggles Body language = rudeness Professional pride over communication mishaps Lack of training on autism Lack of time Pharmacists are vital in autism Need medication, but higher rate of adverse effects Bridge the gap for primary care Non-psychiatric medications Be willing to be the expert

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57 Factors affecting experiences with healthcare Autism-related Provider-level System-level Verbal communication skills Literalness Sensory sensitivities Body awareness Lack of knowledge about autism Attributing all symptoms/behaviors to autism Equating communication to IQ Unwillingness to communicate in writing Skill in incorporating supporters Organization trouble in navigating system Stigma about autism Societal issues with employment/insurance

58 Recommendations from study participants to healthcare providers Respect the way I need to communicate with you Dim lights Don t use open-ended or vague questions Find out how your patient s needs are unique Advocate for your patients Information Navigating healthcare Aids to help prepare for interacting with providers Where to find good information Rights in healthcare

59 Tools for communication Time Remember the diagnosis

60 Review: Autism Spectrum Disorder Diagnosis Deficits in social communication interactions (3/3 required) Social-emotional reciprocity Non-verbal communication Developing, maintaining, and understanding relationships Restricted, repetitive behavior, interests, or activities (2/4 required) Stereotyped or repetitive motor movements, use of objects, speech Insistence on sameness/ritualized behavior Restricted, fixated interests Hypo-hyperreactive to sensory input Present in early development, but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life Cause clinically significant impairment in functioning

61 Give me some space Turn down the noise and the lights Listen for the message behind the behavior Tips for communication in autism Communicate your message clearly Don t use openended questions Write or use pictures Give choices to give control Change your approach Be patient. Honor special interests ocali.org/up_doc/tips_for_supporting_individuals_with_asd

62 Tips for communication in autism Give me some space Turn down the noise and the lights Listen for the message behind the behavior Communicate your message clearly Write or use pictures Change your approach Don t use open-ended questions Give choices to give control Be patient. Honor special interests

63 Conclusion

64 Take home points Autism diagnosis: impaired social communication; restrictive, repetitive behavior or interests Prevalence is increasing, but services are struggling to keep pace Medications are effective for comorbidities, but more likely to cause side effects Communication requires time and keeping the diagnosis in mind

65 Autism