1 MEDICATON MANAGEMENT OF SIDE EFFECTS WHEN ADHD PATIENTS ARE CO MORBID FOR ASPERGER S SYNDROME OR ANXIETY DISORDERS
2 EDWARD B. AULL, M.D N. MERIDIAN SUITE 354 CARMEL, INDIANA FAX BEHAVIORAL PEDIATRICS
3 DISCLOSURE I have no actual or potential conflict of interest in relation to this program/presentation.
4 DISCLOSURES Grant/Research support: none Speaker s Bureau: None in the past three years. Consultant: None in the past five years. Major Shareholder: none I published a book related to this topic entitled, The Parents Guide to the Medical World of Autism.
5 DISCLOSURES I will be discussing the use of SSRI s such as Paxil, Prozac, Zoloft, Celexa, Lexapro in the care of autism for which they are not approved, however they are approved for use in anxiety and depression for which their use will be discussed. I will be discussing the use of atypical antipsychotics two of which are approved for the treatment of autism spectrum disorders, but others have not yet been approved. I will be discussing the use of ADHD medications in autism for which they are not FDA approved but their usage will be discussed in the treatment of ADHD symptoms for which they are approved.
6 DSM-IV 1994 PERVASIVE DEVELOPMENTAL DISORDERS AUTISM, ASPERGER S SYNDROME, PDD-NOS RETTS CHILDHOOD DISINTEGRATIVE DISORDER DID NOT ALLOW ASD AND ADHD
7 DSM AUTISM SPECTRUM DISORDERS ELIMINATES ASPERGER S SYNDROME AND PDD- NOS WILL HAVE SEVERITY ASSESMENTS WILL ALLOW COMORBIDITIES SUCH AS ADHD AND ANXIETY DISORDERS ONE LINE SUGGESTS THOSE FORMERLY CALLED ASPERGER S.
8 CO MORBID DISORDERS THREE FOURTHS OF PATIENTS WITH AUTISM SPECTRUM DISORDERS MEET CRITERIA FOR OTHER PSYCHIATRIC DISORDERS ADHD, ANXIETY DISORDERS, AFFECTIVE DISORDERS BRERETON, ET AL 2006
9 ASD I DEFINE AUTISM SPECTRUM DISORDERS AS A MIX OF ADHD, ANXIETY, AND A LANGUAGE- BASED LEARNING DISABILITY, IN THAT THEY TAKE LANGUAGE TOO LITERALLY, AND DON T READ BODY LANGUAGE WELL
10 ASD PATIENTS WITH ASD S ARE TYPICALLY VERY SENSITIVE TO EVEN SMALL DOSAGE CHANGES OF MEDICATIONS OUTCOMES SUCH AS SEDATION AND ACTIVATION MAY BE QUITE VARIABLE CAUSE OF UNIQUE REACTIONS IS UNKNOWN
11 ASD ADHD AND ANXIETY ARE SEEN AS COMORBIDITIES IN 30 TO 85% OF PATIENTS WITH ASD S IN MANY STUDIES RECENT STUDY (HANSON, ET AL 2013) SHOWED AN INCIDENCE OF ADHD OF ONLY 2-16%, HOWEVER, TYPICAL ADHD QUESTIONAIRES WERE NOT UTILIZED, USED CBCL
12 White Matter Microstructure Predicts Autistic Traits in ADHD Cooper, et. al. J. Autism Dev Disord ( Nov 2014) Cardiff Univ. School of Medicine White matter micostructural signature of autistic traits in ADHD. Abnormal sociocommunicative traits in ADHD appear to have association with the neurobiology of phenotypic variation in ADHD even in those who do not have a known ASD diagnosis.
13 ADHD MEDICATIONS STIMULANT MEDICATIONS WORK PRIMARILY THROUGH INCREASING THE EFFECTS OF DOPAMINE DOPAMINE AGGRAVATES ANXIETY THOSE THAT WORK PRIMARILY THROUGH INCREASING NOREPINEPHRINE, TEND NOT TO INCREASE ANXIETY BUT THEY DO NOT IMPROVE IT EITHER
14 ADHD MEDICAITONS IN ASD MOST STUDIES IN PATIENTS WITH ASD S SHOW LESS ROBUST EFFECTS ON ADHD AND GREATER INCIDENCES OF SIDE EFFECTS AND MORE SIGNIFICANT SIDE EFFECTS
15 Pharmacological treatment of ADHD in PDD Meta-analysis of seven trials with 225 children Methylphenidate is effective with increased side effects including decreased appetite, depression, insomnia, irritability, and social withdrawal Clonidine and atomoxetine may be effective. Reichow, Volkmar, Bloch JADD 2013
16 EFFECT SIZE If tested at two standard deviations off the norm, receives treatment, and then tests one standard deviation off the norm, that is an effect size of one. Average effect size for psychiatric medications is about 0.33
17 TRUE AMPHETAMINES Amphetamines, Adderall, Vyvanse, Dexedrine, Procentra, have the greatest effect size, about 0.9 to 1.2 They also tend to have the most side effects The most even release will likely have the least side effects. In this group Vyvanse is the most even release Two new drugs, one dextroamphetamine salts in more doses, Zenzedi, 5,7.5,10,15,20,30 mg. Second is a mix of dextroamphetamine and levoamphetamine salts, Evekeo, 5,10 mg.
18 AMPHETAMINE EFFECTS Adderall IR 4 to 5 hours Dexedrine IR 4 to 5 hours Adderall XR 11 to 12 hours at appropriate dose Vyvanse 13 to 16 hours at appropriate dose Dexedrine Spansule 8 to 9 hours Patients may be crabby at peak dose or when medication is wearing off
19 AMPHETAMINE SIDE EFFECTS Decreased appetite and interference with sleep tend to be more severe than other stimulants, however, for the great majority of patients, these issues are only significant when first starting the medications Aggravating anxiety, aggravating social quietness, and aggravating lack of tolerance for imperfection in others and sometimes oneself, are common. Anxiety issues may be lessened with the addition of anxiolytic medications such as SSRI s
20 METHYLPENIDATES Ritalin, Focalin, Metadate, Methylin, Daytrana, Quillivant, have effect size of 0.7 to 1.0 Ritalin LA and Focalin XR release 50% morning and lunch Metadate, Concerta, and Quillivant release about 25% at first and about 75% four hours later Daytrana is the most even release and may therefore have less side effects
21 METHYLPHENIDATE SIDE EFFECTS Decreased appetite and interference with sleep tend to be less significant than with true amphetamines 30% of patients may actually have better sleep initiation if their medication is still working and don t have rebound racing thoughts Most patients will suffer less social quietness and pressuring of anxiety on methylphenidates than on amphetamines but some patients are more social on the amphetamines
22 METHYLPHENIDATE EFFECTS IR Ritalin 2.5 to 4.0 hours IR Focalin 4 to 5 hours Concerta 11 to 12 hours at correct dose Daytrana 10 to 12 hours Metadate CD and Focalin XR, 8 to 9 hours May be a rebound sensitivity, easily upset or tearful as the dose wears off
23 NONSTIMULANTS Strattera, Intuniv, Kapvay Last all day Do not aggravate anxiety or social quietness, in fact, may help with social interest and reading social cues Not as potent as the stimulants, Intuniv and Kapvay are often used as adjuncts with a stimulant Sleepiness is the main negative side effect and is variable from person to person May be drugs of preference in patients with autism spectrum disorders
24 OTHER ADHD MEDICATIONS Wellbutrin, Remeron, tricyclics such as imipramine or desipramine May be as potent as a stimulant, but not often Do help with anxiety, appetite, and sleep(?) Tricyclics may be fatal in overdose Vayarin? Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA)
25 ANXIETY 40% of children with ASDs fulfill diagnostic criteria for an anxiety disorder. Van Steensel et al % have impairing anxiety symptoms. White et al Co-occurring anxiety can cause acute distress, amplify the core symptoms of ASD, and trigger behavioral difficulties, including tantrums, aggression and self injury. Canitano 2006
26 ANXIETY AND ADHD STIMULANTS CAN BE USED BUT THE ANXIETY MUST BE PROTECTED USUALLY WITH THE USE OF AN SSRI. IN ASD THE ANXIETY MAY HAVE TO BE TREATED PRIOR TO THE INITIATION OF A STIMULANT. IF THE ANXIETY IS IMMEDIATELY INCREASED WITH A SMALL DOSE OF A STIMULANT, AN ASD SHOULD BE CONSIDERED.
27 ANXIETY SSRI S ARE THE PRIMARY MEDICATIONS USED TO IMPROVE ANXIETY PROZAC, ZOLOFT, AND LEXAPRO ARE FDA APPROVED IN CHILDREN BENZO S SHOULD BE AVOIDED EXCEPT FOR SHORT EVENTS SUCH AS DENTAL VISIT, PLANE TRIP, DELIVER A SPEECH
28 ANXIETY Goals of SSRI treatment: 1 less anxiety, less obsessive behavior, easier transitions 2 better eye contact, better reciprocal conversations 3 disinhibition, so that they can or will do what others want them to do
29 ANXIETY ANXIETY MAY HIDE ADHD, PATIENT WANTS TO PLEASE, NOT BREAK RULES AS ANXIETY IS LOWERED WITH SSRI, MAY EXPOSE ADHD SSRI S DO NOT HAVE ADHD EFFECTS, IF IMPROVED ATTENTION IS NOTED, ANXIETY WAS INTERFERING WITH ATTENTION, RATHER THAN A DIRECT EFFECT ON ATTENTION SNRI S HAVE SOME ADHD EFFECTS
30 ANXIETY ATYPICAL ANTIPSYCHOTICS MAY HAVE TO BE USED TO AUGMENT ANTIANXIETY EFFECTS OF SSRI S. ATYPICAL ANTIPSYCHOTICS MAY IMPROVE SOCIAL INTEREST AND READING OF SOCIAL CUES IN ASD S. ATYPICAL ANTIPSYCHOTICS MAY BE USED FOR OPPOSITIONAL SYMPTOMS AND TICS. GUANFACINE AND CLONODINE MAY OBVIATE THE NEED FOR AN ATYPICAL ANTIPSYCHOTIC.
31 ATYPICAL ANTIPSYCHOTICS Abilify and Risperdal are FDA approved for treatment of aggression and outbursts in autism spectrum disorders Zyprexa, Seroquel, Geodon, Saphris, Fanapt are also used Antipsychotics augment SSRI s in treatment of anxiety and depression Main side effects are weight gain and potential for tardive dyskinesia Effects are quite variable from patient to patient
32 ASD IF ONLY TREAT ADHD, ESPECIALLY WITH STIMULANTS, OFTEN MEDICATON WILL WORK FOR ONLY A FEW MONTHS, OR ANXIETY WILL BE INCREASED AND THE PATIENT WILL GET WORSE TREATING ANXIETY FIRST MAY BE REQUIRED TO TOLERATE ANY DOSE OF A STIMULANT BUT ESPCIALLY A ROBUST DOSE IF REQUIRED FOR ADHD SYMPTOMS
33 ASD THE MORE EVEN THE MEDICATION WILL RESULT IN LESS SIDE EFFECTS. VYVANSE AND DAYTRANA ARE VERY SMOOTH ISOMERS LIKE FOCALIN AND LEXAPRO TEND TO HAVE LESS SIDE EFFECTS NONSTIMULANTS MAY BE PREFERRED IN PATIENTS WITH ASD AND MAY IMPROVE INTEREST IN SOCIAL INTERACTION AND READING OF SOCIAL CUES.
34 SOCIAL ISSUES WITH STIMULANTS AGGRAVATE ANXIETY AGGRAVATE SOCIAL QUIETNESS AGGRAVATE LACK OF TOLERANCE FOR IMPERFECTION IN OTHERS THESE ISSUES ARE ALSO SEEN IN PATIENTS WITH ADHD BUT MAY BE MORE SEVERE OR MORE DEBILITATING IN ASD
35 PATS STUDY Preschool children and treatment with ADHD medications. 76.5% of children had one other diagnosis 29.7% of children had two or more additional diagnoses.