Comorbid Conditions in Autism Spectrum Illness. David Ermer MD June 13, 2014



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Comorbid Conditions in Autism Spectrum Illness David Ermer MD June 13, 2014

Overview Diagnosing comorbidities in autism spectrum illnesses Treatment issues specific to autism spectrum illnesses Treatment options with emphasis on pharmacology

Autism and Comorbidity 64 % poor attention and concentration 36-48% hyperactive 43-88% morbid or unusual preoccupation 37% obsessions 16-18% compulsions or rituals 50-89% had stereotyped utterance 68-74% stereotyped movements

Autism and Comorbidity (cont) 17-74% had anxiety or fears 9-44% irritability, agitation 24-43% self injury 8% motor or vocal tics 5 % seizures

Comorbidity vs Associated Features Research on the specific relationship between these associated features and autism is sparse. Is it truly a comorbid illness or part of autism? Preoccupations, anxiety, lack of concern regarding activity, stereotypies can all appear as ADHD

Assessing Children With Autism Spectrum Disorder and Comorbidity Careful history gathering Observations from multiple settings Multidisciplinary evaluation is essential Information on prior interventions

Diagnostic Dilemma Even after careful evaluation, it may be impossible to determine if the symptoms constitute a comorbid Ilness Must establish treatment priorities

Considerations for Treatment Priorities Symptoms that threaten the safety of patient, family members or others Symptoms that generate subjective distress for the patient Symptoms that are sources of adversity in the family s life Symptoms that jeopardize sustained education progress

Must Characterize Symptoms Distribution Intensity Onset: Time and location Duration Ameliorating Factors Aggravating Factors

Treatment Issues in Autism Spectrum Illnesses Building relationships and gaining trust can be difficult Many of the difficulties are more distressing for the people around the patients than the patient themselves The patient may have trouble identifying their own internal mood state

Treatment Issues (cont) Patient difficulty in understanding people s intentions, wishes, and needs Weaknesses in ability to observe sequence of events and logical responses; flawed sense of proportion, highly concrete Patients are often rigid and inflexible with treatment interventions

Treatment Strategies for Pharmacologic Intervention Educational and behavioral supports are the mainstays of treatment Pharmacologic treatments are available and significantly beneficial It is essential to integrate behavioral and pharmacologic treatments Focus on Target Syptoms vs Diagnosis

Realistic Expectations Must be Set Expectation that symptoms remit more quickly with pharmacologic treatment over behavioral treatments Expectation that response will be more complete with pharmacologic treatments magic bullets

Must Optimize Environment Evaluate school setting Work with caregivers on home environment Pharmacologic strategies ineffective in unsupportive and inadequate environments

Parental Collaboration is Essential Monitor patient and provide information to provider Administer medication Observe side effects Note emotional and behavioral effects Collaborate their information with school

Focus on Symptom Clusters Most of the core symptoms are likely to remain Must focus on specific measurable symptoms The clinician s goal is a reduction in the specific symptoms that interfere with functioning Unlikely that medications will improve skills

Side Effects Side effects are more likely for all medicines used in autism spectrum disorders; greater variety and rate due to atypical sensory world May find even minor side effects impossible to tolerate They may be less likely to report side effects Highly concrete patients may need to be asked about specific side effects

Medication Indications in Autism Spectrum Illnesses No medication influences core pragmatic social skill Absence of high quality valid studies Absence of studies in autism with comorbid conditions (Almost all treatment studies with medication in childhood disorders exclude autism spectrum illnesses)

Target Symptoms for Medications Hyperactivity and Attention Problems Impulsivity Anxiety including Social Anxiety Obsessive-compulsive symptoms Tics Depression

Medication Target Symptoms (Cont.) Stereotypies Mood Swings Agitation Aggression Self Injury Insomnia

Trends in Medication Use In one study 55% of Autistic individuals were taking a psychotropic medication 29.3% were on two or more medications Antidepressants were most common 32.1% Stimulants next most common 20.2% Followed by neuroleptics 16.5%

Stimulant Medications Useful for hyperactivity, attention, and impulsivity 49% response rate (lower than children without autism 60%) 18% had intolerable side effects (much higher than children without autism) Side effects more common in autism include irritability, stereotypy, and self injury

Atomoxetine 43% response rate for ADHD symptoms Heterogeneous response with some doing quite well Less serious adverse side effects such as irritability Stomach upset was most common side effect

Alpha II Agonists (Clonidine, Tenex, Intuniv) Several small studies showed significant improvement over placebo in hyperactivity Sedation is major side effect with clonidine Less irritability than stimulants Clonidine can be helpful at night for sleep

Neuroleptics Risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa), aripiprazole (Abilify) Used for tics, mood swings, stereotypies, aggression, self injury, obsessions All have potential for movement disorders as long term side effects

Risperidone FDA approved for treatment of irritability associated with autistic disorder in children and adolescents, including symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums and quickly changing moods. Studies also showed improvement in stereotypic behaviors and hyperactivity Lack of clear benefit of core symptoms

Risperidone Side effects include weight gain, increased appetite, fatigue, drooling, tremor, constipation, increased prolactin Authors of RUPP study concluded that risperidone should be reserved for treatment of moderate-to-severe behavioral problems associated with autism

Aripiprazole (Abilify) FDA approved for irritability associated with autism Weight gain, fatigue, restlessness can be side effects

Serotonin Reuptake Inhibitors Sertraline, fluoxetine, citalopram, etc Helpful in depression, anxieties, obsessive-compulsive behavior, anger Can be activating and disinhibiting

Mood Stabilizers Valproic acid (Depakote), carbamazepine (Tegretol), Lithium etc Used for mood swings, self injury, aggression

Melatonin Supplement used for sleep

Conclusions Paucity of studies in autism spectrum disorders and comorbidity making diagnoses quite difficult Behavioral interventions are first line Must have clear, realistic, measurable target symptoms Lower response rate and more side effects with medication management in autism spectrum disorders

Sources RUPP Autism Network (2002) Risperidone in children with autism and serious behavior problems, New England Journal of Medicine 347:314-321 Arnold et al (2006) Atomoxetine for hyperactivity in autism spectrum disorders: Placebo-Controlled Crossover Pilot Trial, J Am Acad Child Adol Psychiatry 45:1196-1205 Towbin K, Strategies for pharmacologic treatment of high functioning autism and Asperger syndrome (2003) Child and Adolescent Clinics of North America 12:23-45