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Autism Spectrum Disorders:
Pharmacological OptionsDr Jane McCarthy MD MRCGP FRCPsych
Consultant Psychiatrist in Intellectual Disability
East London NHS Foundation Trust & King’s College London, UK
NADD International Congress, Miami, 2014 Challenges
• Assessment and diagnosis
• Lack of psychopharmacological research
• Coordinating behavioral and social interventions with pharmacotherapy
• Capacity issues
Autism Spectrum
Disorders
Core symptoms of ASD:• Deficits in Social Communication & Social Interaction• Restricted & repetitive behaviour, interests or activities
No medication shown to impact on the core symptoms of ASD• Psychosocial Interventions for
�For core symptoms� For life skills
Neurochemical
abnormalities
• Increased Serotonin (~ 30% affected)
• Altered developmental trajectory of brain serotonin synthesis capacity
• Reduction in GABA synthetic enzymes & receptors (Inhibition)
• Glutamate (imbalance of excitatory: inhibitory ratio)
• Oxytocin & Vasopressin linked to Social behaviours
No evidence for treatment
of core symptoms
• Anticonvulsants• Chelation• Exclusion diets• Vitamins, minerals and dietary supplements• Drugs specifically designed for cognitive functioning• Oxytocin• Secretin• Testosterone regulation• Hyperbaric oxygen• Antipsychotic medication• Antidepressant medication
Use of medication
• Use to manage associated symptom behaviours such as• Aggression
• Irritability
• Self-Injury
• Hyperactivity
• Impulsivity
• Sleep problems
• Repetitive behaviours
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Use of medication:
comorbidity
• ADHD (28-44%)
• Obsessions, rituals, OCD (7-24%)
• Anxiety (42-56%)
• Mood disorders – depression, cyclical (up to 70%)
• Psychotic symptoms (12-17%)
• Tics/ Tourette’s disorders (14-38%)
Evidence base
• Good quality evidence is sparse, does not mean it is ineffective
• Evidence was based on case studies instead of RCTs
• Lack of studies directly comparing different medication to manage specific behavior problems
• 45% of Adults with ASD on psychotropic medication (Langworthy-Lam et al., 2002)
Atypical Antipsychotics
• Risperidone – irritability, aggression, hyperactivity and Self-injurious behaviour (Most evidence & approved by FDA for treating irritability)
• Aripiprazole –FDA approval for irritability
• Ziprasidone – reported benefits
• Olanzapine & Quetiapine – no strong evidence
• Psychotic symptoms
• Schizophrenia
Atypical Antipsychotics
• Start medication at a low dose & gradually increase until there is an improvement or until adverse effects are displayed.
• Prescribe at a dose that does not exceed the BNF recommended max.
• Prescribe medication for a minimum period of time necessary and at a minimum effective dose to manage the behavior problems.
Consider all therapeutic options
Selective Serotonin
reuptake inhibitors
• Fluoxetine slight evidence that reduce repetitive behaviours
• Escitalopram, Tianeptine & Fluvoxamine
• Self-injurious behaviour- no evidence
• No effect on social impairments
• In combination with CBT for anxiety disorders
• Treatment of OCD
Antiepileptics
• Divalproex sodium – Irritability, compulsive behaviours
• Lamotrigine ( inhibits glutamate release)
• Levetiracetam – no supporting evidence
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ADHD symptoms
• Large scale RCT, methylphenidate is less effective in children with ASD
• More at risk from side effects of irritability, irritability, stereotypies, sleep disturbance
• Lower doses with careful clinical monitoring
• Atomexitine in adults
• Antipsychotics
Other medications
• Anxiolytics – Buspirone, Pregabalin
• B-Blockers
• Naltrexone
• Clonidine & Guanfacine
• Amantidine• No Good Evidence to use the above
• Melatonin for Sleep problems (BMJ: November 2012)
Prescribing Issues
• Monitor side effects
• Idiosyncratic reactions
• Can sometimes worsen behaviours
• Used only in combination with other therapeutic approaches
• Specialist clinics for complex regimes e.g. experimental drugs or polypharmacy
• > Benefits to Risk Ratio
Capacity & Compliance
Input from the Person with ASD and carer/family
• Communicate the information with ASD in a way they can understand e.g. may require the use of innovative methods such as using pictures
• Prescribe the medication at a time of day that minimizes the need for administration in multiple settings
• Prescribe one medication at a time
Case Scenario 1
• 22 year old man
• Mild ID & ASD
• Never sits still
• Impulsive & episodes of physical aggression to others
• ? Any role for medication
Case Scenario 2
• 30 year old man
• Severe ID & ASD
• Unprovoked physical aggression to others
• Periods of irritability
• Any role for medication?
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Future Trends in
Prescribing
• Combining drugs with other interventions
• Optimal doses to use
• Larger RCTs which make comparisons
• Longer term Efficacy & Safety studies
• Newer drugs e.g. Oxytocin, Cholinergic agents,
r-Baclofen, Glutamatergic agents
References
Broadstock et al., (2007). Systematic review of the effectiveness of pharmacological treatments for adolescents and adults with autism spectrum disorder. Autism, 11, 335-348.
Wink et al., (2010). Emerging drugs for the treatment of symptoms associated with autism spectrum disorders. Expert Opinion on Emerging Drugs. 15, 481-494.
NICE Clinical Guidelines Number 142: www.nice.org.uk
Cantiano R & Scandurra V (2011). Psychopharmacology in autism: An update. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 35, 18 -28.
Lai MC et al., (2014). Autism. Lancet, 383, 896-910.