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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.