Anxiety, Sleep & Attention - Treatment in Autism. Presentation Topics. Patient Case 5/4/2015

Transcription

1 Anxiety, Sleep & Attention - Treatment in Autism Dr. Rowena Moore, CCC-SLPD Presentation Topics Patient case Behavioral Concerns Autism - Characteristics Autism - Management C.J. s Medications Literature Review Medication Interactions Personalized Medicine Epocrates 2 Patient Case 9 year old white male Significant speech delays Said his first word at 2 ½ years old Preschool Disabled 2004 Pervasive Developmental Disorder 2004 Autism Spectrum Disorder (ASD) 2006 Difficulty chewing and had frequent vomiting episodes Anxiety - low noise tolerance Current placement - self-contained Multiply Disabled 4 th / 5 th grade classroom Speech 4X week OT 2X week 3 1

2 Behavioral Concerns Anxiety Perseverative behaviors topics, skin picking, vocal noises Sensory feeding issues Poor attention 4 ASD - Characteristics DSM-IV Criteria: 6 or more items from (1, 2, & 3) 1. Deficits in social interaction poor eye contact, inability to develop relationships with peers, lack of interest in others 2. Deficits in communication delayed or abnormal language, inadequate conversational skills, restrictive or stereotypical language and play 3. Limited, repetitive behaviors and activities and resistance to change. (American Psychiatric Association, 1994) 5 ASD - Management Behavioral Interventions 1:1 behavioral interventions - (Eskeseth, Smith, Jahr, Eldevik, 2007) Cognitive Behavior Interventions - to develop social functioning (Lopata, Thomeer, Volker, & Nida, 2006) Pharmacological Interventions Most common classes of medications include: Antipsychotics, psychostimulants, anxiolytics, hypnotics, antidepressants, antihypertensives, and mood stabilizers. (Posey & McDougle, 2001) 6 2

3 Medications & Behavior Clusters ADHD-type Symptoms Psychostimulants: Methylphenidate, (RUPP, 2005a) Antidepressants (Venlafaxine) α 2 Adrenergic Agonists (Clonidine*) Alzheimer s Disease Therapeutics (Doyle et. al., 2006) 7 Medications & Behavior Clusters Aggression, irritability, and self-injurious behaviors Typical Antipsychotics: Haloperidol (Campbell et. al., 1982) Atypical Antipsychotics: Risperidone (Research Units on Pediatric Psychopharmacology Autism Network, 2005b) Antiepileptic Topiramate (Hardan & Harden, 2004) 8 Medications & Behavior Clusters Stereotypic/Repetitive Behaviors Selective Serotonin Reuptake Inhibitors (SSRIs) Fluvoxamine* Other Treatments Mood stabilizers Alternative treatments Secretin (Sandler et. al., 1999) Vitamin supplements (Bolman & Richmond, 1999) 9 3

4 Case Study Fluvoxamine (Luvox) (anxiety) 90 mg Clonidine (sleep) 0.2mg Lisdexamfetamine(Vyvanse) (ADHD) 50 mg 10 C.J. s Medication Modifications PAST Clonidine, Luvox, Focalin XR Improvements in sleep Reduction in anxiety but occasional gagging & vomiting Internally distracted/disconnected Stereotypical behaviors self talk, giggling Datrayna Patch adverse effects allergic skin rash CURRENT: Clonidine, Luvox, Vyvanse Gagging & vomiting stopped Hand picking stopped and ear rubbing reduced Decrease in attention after lunch and increase in vocal noises/self talk 11 Some internal distractions but more engaging Fluvoxamine (Luvox) Selective serotonin reuptake inhibitor (SSRI) First developed as an antidepressant but used to treat social anxiety disorder, obsessive compulsive disorder, panic disorder Little effect on dopamine and norepinephrine Binds to σ1 receptors Potent inhibitor of CYP1A2 Moderate CYP3A4 & CYP2C19 Half-life 15 hours Steady state 10 days Metabolism liver (Clinical Pharmacology, 2011c, Irons, 2005) Excretion Urine Breast milk minimal (Piontek, Wisner, Perel, & Peindle, 2001) (Irons, 2005) 12 4

5 Fluvoxamine Possible side Effects Headaches Asthenia Somnolence Insomnia Nervousness Dizziness Tremor Anxiety Hypertonia Agitation Vasolidation Sweating Chills Depression CNS stimulation Change in taste Palpitations GI disturbance Dysphagia** Dry mouth Sexual dysfunction Urinary disorder Upper respiratory tract infection Dyspnea Yawning (Vogel, Carter, & Carter, 2000, p. 152) 13 Fluvoxamine (Luvox) 10-week, prospective, open-label design 18 subjects with Autistic Disorder, Asperger Syndrome or Pervasive Developmental Disorder, 7 to 18 years old Fluvoxamine dosage of 12.5 or 25mg based on weight Weekly adjustments 12.5 or 25 mg (Martin, Koenig, & Scahill, 2003) 14 Efficacy of Fluvoxamine Primary Efficacy: Clinical Global Impression Scale (CGIS) Overall changes not significant Secondary Efficacy: Children s Yale Brown Obsessive Compulsive Scale (C-YBOCS) & Screen for Child Anxiety Related Emotional Disorders (SCARED) Decrease in anxiety and obsessive compulsions were small 3 subjects made significant improvements 5 subjects made partial improvements Limitations: Small sample size No control group Respondents could not report symptoms (Martin, Koenig, & Scahill, 2003) 15 5

6 Clonidine (Catapres) Clonidine has antihypertensive elements (Mehta, Patel, & Castello, 2004) Alpha-2 adrenergic receptor agonist Metabolized: liver, excreted: urine and feces, peak concentration: 3-5 hrs., and half-life: hrs. (Clinical Pharmacology, 2011a); CYP450: Unknown Used to treat Attention Deficit Hyperactivity Disorder (Scahill, 2009) Tourette s syndrome, panic disorder, posttraumatic stress disorder (Fankhauser et. al. 1992) Sleep problems (Ingrassia & Turk, 2005) 16 Clonidine Adverse Effects Drowsiness Dry mouth and nose Constipation Decreased heart rate Mild orthostatic hypotension Dizziness Fatigue Anxiety Nervousness Dryness and burning of the eyes Painful parotid gland Nausea Vomiting Weigh gain Urinary retention (Vogel, Carter, & Carter, 2000, p. 100) 17 Efficacy of Clonidine (Catapres) Open-label, semi-quantitative study ( ) 17 children with ASD, PDD, and Asperger s Disorder Initial bedtime dose was 0.05 mg and slowly advanced to 0.1 mg once a day Caregivers recorded estimated Hours of sleep and Night time awakenings before and after treatment Behavioral improvements (Ming, Gordon, Kang, & Wagner, 2008) 18 6

7 Clonidine (Catapres) Results: Improvements in 16 children with sleep initiation problems Improvements in 16 of the 17 children with sleep maintenance problems 5 subjects experienced night awakenings A variety of improvements in behaviors reported Limitations: It was a retrospective, open-labeled study Study was based on parent estimation (Ming, Gordon, Kang, & Wagner, 2008) 19 Lisdexamfetamine (Vyvanse) Stimulant for treating ADHD adults and children Long-lasting prodrug Blocks reuptake and facilitates the release of dopamine and norepinephrine (Mattingly, 2010) It is converted to l-lysine and d-amphetamine Conversion is mainly in the blood (Turgay et. al., 2009) CYP450:2D6 (weak inhibitor) Half-life: 6 8 hrs. in children Metabolized: liver Excreted in the urine 96%, feces 0.3% (Clinical Pharmacology, 2011d; Epocrates, 2011) 20 Vyvanse Adverse Effects Difficulty falling asleep Sleepiness Uncontrollable shaking Dizziness Jitters Headache Dry mouth Stomach pain Diarrhea Nausea Vomiting Loss of appetite Weight loss Fever Sweating (National Center for Biotechnology Information, 2011) 21 7

8 Efficacy and Tolerability of Vyvanse Phase III, multi-center (40), randomized, double-blind, forced-dose, parallel-group study 290 boys and girls between the ages 6 to 12 with ADHD 6 week study in 3 phases Phase 1 screening Phase 2 Washout Phase 3 4 weeks double-blind study Group 1 30 mg/4 weeks Group 2 50 mg (30 mg/week 1 with forced-dose to 50mg/week 2-4) Group 3 70mg (30 mg/week1, 50 mg/week 2, 70 mg/week 3 & 4) Group 4 Placebo capsules (Biederman, Krishnan, Zhang, McGough, & Findling, 2007) 22 Efficacy and Tolerability of Vyvanse Results: ADHD Rating Scale IV 70mg group showed the greatest gains, p <.001 Conners Parent Rating Scale Revised: Short Form Subjects showed improvements throughout the day 70mg group showed the greatest improvements Clinical Global Impressions Scale 70% much improved or very much improved Adverse effects: Tolerability Assessments 95% mild to moderate adverse effects Limitations: Four weeks insufficient to determine the long-term effects Findings based on parent assessments (Biederman, Krishnan, Zhang, McGough, & Findling, 2007) 23 Major risk requires monitoring Drug Interactions Clonidine (Clinical Pharmacology, 2011b) Vyvanse Luvox 24 8

9 Personalized Medicine No longer one size fits all DNA Testing Mayo Clinic NIH website Epocrates Questions 9

10 American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM_IV). Washington, DC: American Psychiatric Association. Biederman, J., S. Krishnan, Zhang, Y., McGough, J. J., Findling, R. L. (2007). Efficacy and tolerability of Lisdexamfetamine Dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: A Phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study. Clinical Therapeutics, 29(3): doi: /s (07)80083-x Bolman, W. M. & J. A. Richmond (1999). A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. Journal of Autism & Developmental Disorders, 29(3): Campbell, M., Anderson, L. T., Small, A. M., Perry, R., Green, W. H., & Caplan, R. (1982). The effects of Haloperidol on learning and behavior in autistic children. Journal of Autism and Developmental Disorders, 12(2), doi: /bf Clinical Pharmacology (2011a). Clonidine. Clinical Pharmacology. Retrieved from ip.com.ezproxylocal.library.nova.edu/forms /drugoptions.aspx?cpnum=139&n=clonidine Clinical Pharmacology (2011b. Drug interaction report for healthcare professionals. Clinical Pharmacology. Retrieved from 9,265,3571&l=0 Clinical Pharmacology (2011c). Fluvoxamine. Clinical Pharmacology. Retrieved from /Monograph/monograph.aspx?cpnum=265&sec=monadve Clinical Pharmacology (2011d). Lisdexamfetamine. Clinical Pharmacology. Retrieved from /Forms/Monograph/monograph.aspx?cpnum=3571&sec=monphar 29 Doyle, R. L., Frazier, J., Spencer, T. J., Geller, D., Biederman, J. & Wilens, T. (2006). Donepezil in the treatment of ADHD-like symptoms in youths with Pervasive Developmental Disorder: A case series. Journal of Attention Disorders, 9(3), doi: / Eikeseth, S., Smith, T., Jahr, E., & Eldevik, S. (2007). Outcome for children with autism who began intensive behavioral treatment between ages 4 and 7: A comparison controlled study. Behavior Modification, 31 (3), Epocrates Vyvanse. Retrieved from showpage.do?method=drugs&monographid=4678&activesectionid=10 Fankhauser, M. P., Karumanchi, V. C., German, M. L., Yates, A., & Karumanchi, S. D. (1992). A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in Autism. Journal of Clinical Psychiatry, 53(3), Hardan, A. Y., You, R. J., Hardan, B. L. (2004). A retrospective assessment of Topiramate in children and adolescents with Pervasive Developmental Disorders. Journal of Child and Adolescent Psychopharmacology, 14(3), doi: /cap

11 Ingrassia, A. and J. Turk (2005). The use of clonidine for severe and intractable sleep problems in children with neurodevelopmental disorders. European Child & Adolescent Psychiatry, 14(1): doi: /s Irons, J. (2005). Fluvoxamine in the treatment of anxiety disorders. Neuropsychiatric Disease and Treatment, 1(4) Lopata, C., Thomeer, M. L., Volker, M. A., Nida, R. E. (2006). Effectiveness of a Cognitive-Behavioral Treatment on the social behaviors of children with Asperger Disorder. Focus on Autism and Other Developmental Disabilities 21 (4), doi: / Martin, A., K. Koenig, Anderson, G. M., & Scahill, L. (2003). Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders: A prospective, open-label study. Journal of Autism & Developmental Disorders, 33(1), Mattingly, G. (2010). Lisdexamfetamine Dimesylate: A prodrug stimulant for the treatment of ADHD in children and adults. CNS Spectrums. Retrieved from 31 Mehta, U. D., Patel, I., & Castelle, F. (2004). EEG sedation for children with autism. Developmental and Behavioral Pediatrics, 25(2), doi: / Ming, X., Gordan, E., Kang, N., & Wagner, G. C. (2008). Use of clonidine in children with autism spectrum disorder. Brain & Development, 30(7), doi: /j.braindev National Center for Biotechnology Information. (2011). Lisdexamfetamine. PubMed Health. Retrieved from /druginfo/meds/a html Piontek, C. M., Wisner, K. L., Perel, J. M., Peindl, K. S. (2001). Serum Fluvoxamine levels in breastfed infants. Journal of Clinical Psychiatry, 62(2), doi: /jcp.v62n0207 Posey, D. J. & C. J. McDougle (2001). Pharmacotherapeutic management of autism. Expert Opinion on Pharmacotherapy, 2(4), doi: / Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. (2005a). Randomized, controlled, crossover trail of Methylphenidate in pervasive developmental disorders with hyperactivity. Archives of General Psychiatry, 62(11), Research Units on Pediatric Psychopharmacology Autism Network (2005b). Risperidone treatment of autistic disorder: Longer-term benefits and blinded discontinuation after 6 months. The American Journal of Psychiatry, 162(7), Sandler, A. D., Sutton, K. A., DeWeese, J., Girardi, M. A., Sheppard, V., & Bodfish, J. W. Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder. New England Journal of Medicine, 341(24), doi: /nejm Scahill, L. (2009). Alpha-2 adrenergic agonists in children with inattention, hyperactivity and impulsiveness. CNS Drugs, 23(1), doi: /

12 Turgay, A., Ginsberg, L., Sarkis, E., Jain, R., Adeyi, B., Gao, J., Findling, R. L. (2010). Executive function deficits in children with Attention-Deficit/Hyperactivity Disorder and improvement with Lisdexamfetamine Dimesylate in an open-label study. Journal of Child and Adolescent Pharmacology, 20(6), doi: /cap Vogel, D., Carter, J. E., & Carter, P. B. (2000). The effects of drugs on communication d isorders, 2nd ed. SanDiego, CA: Singular Publish Group