Dr O Papacchini, GWH Swindon 18 November 2015

Introduction How scientific evidence is demonstrated Possible confounding factors when a single patient seems to respond to a certain treatment Safety of treatments Controversies about ASD treatment

RCT (Randomised controlled trial) A randomized controlled trial (RCT) is a type of medical experiment where the people being studied are randomly allocated one or other of the different treatments under study. A RCT contains control groups - no treatment, a placebo-controlled study - a previously tested treatment, a positive-control study

Randomised controlled trial

Placebo effect ‘I will please’ An inactive substance/treatment can sometimes improve a patient’s condition simply because the person has the expectation that it will be helpful To separate out this power of positive thinking from a treatment true medical benefits a placebo-controlled study is necessary The placebo effect is real and powerful and can cause real improvements in health conditions

Anecdotal reports of children affected by ASD improved on ‘unconventional’ treatments Think: Placebo effect? Co-existing undiagnosed condition that responds to that treatment? (Ex: Coeliac Disease -> Gluten free diet) Conflict of interest? (Ex: assessor of progress sells the treatment) Real improvement in a subset of patients?

Speak to a health professional Safety of treatment Objective measurement of improvement Future research

Evidence based interventions Literature review by UK and USA experts Controversies: lack of RCT, but consensus that some of the interventions are likely to be beneficial Need for further research

Evidence based treatments for ASD Carolina Institute for Developmental Disabilities (CIDD) at University of North Carolina LC Politte, et al. Current Treatment Options in Psychiatry, 2015

Pharmacological treatments

Antipsychotics Risperidone Moderate evidence that improves challenging behaviours Significant adverse effects (marked weight gain, sedation, extrapyramidal symptoms, tardive dyskinesia) Aripiprazole High evidence that improves challenging behaviours Significant adverse effects (marked weight gain, sedation, extrapyramidal symptoms, tardive dyskinesia) Significant side effects limit their use to patients with severe impairment or risk of injury

Serotonin-Reuptake Inhibitors and others antidepressants Rarely helpful in alleviating irritability and repetitive behaviours May be helpful for treatment of comorbid anxiety or depression, although evidence is lacking

Stimulants and Atomoxetine in hyperactive children Strength of evidence INSUFFICIENT (Only 1 good quality RCT). Methylphenidate and Dexamphetamine may be used, though children with ASD are more prone to side effects and show a less robust response rate (49% vs 77%) Atomoxetine response rates similar, effect sizes more modest (the larger the effect size, the greater is the impact of an intervention).

Oxytocin This neuropeptide has been associated with the development of social behaviours. Currently clinical studies are in progress. Not recommended at this time

Arbaclofen Memantine N-Acetylcysteine Not recommended due to lack of substantive evidence. Further studies are needed.

Dietary interventions?

Dietary Interventions Gluten-free and casein-free diets : INSUFFICIENT EVIDENCE Risk for nutritional deficiencies or excess: medical advice is recommended

Complementary and alternative medicine

Complementary and alternative medicine (CAM) Up to 50% of families with children with ASD use CAM treatments Clinical trials are lacking to support or refute CAM interventions Medical advice is paramount in establishing safety MELATONIN recommended for sleep onset difficulties MULTIVITAMINS can be considered for children with poor diets SECRETIN not effective (16 RCT)

Hyperbaric oxygen therapy Complications: CNS oxygen toxicity (seizures), barotrauma (tympanic membrane rupture, lung collapse) RCT: only one had a positive significant finding, two subsequent ones did not support the earlier findings At this time it is not recommended

Chelation Approved for detoxification of heavy metals in documented cases, such as in lead poisoning Evidence of chelation benefit in ASD is lacking Clinical trial halted after animal models demonstrated lasting cognitive impairment Deaths reported secondary to hypocalcemia from intravenous chelation using EDTA Chelation is not recommended

Death from chelation therapy Pennsylvania. In August 2005, a boy aged 5 years with autism died while receiving IV chelation therapy with Na2EDTA in a physician's office. During the chelation procedure, the mother noted that the child was limp. The physician initiated resuscitation, and an emergency services team transported the child to the hospital. At the emergency department (ED), further resuscitation was attempted, including administration of at least 1 and possibly 2 doses of IV calcium chloride. Subsequently, the boy's blood calcium level was recorded in the ED as 6.9 mg/dL. The child did not regain consciousness. The coroner examination indicated cause of death as diffuse, acute cerebral hypoxic-ischemic injury, secondary to diffuse subendocardial necrosis. The myocardial necrosis resulted from hypocalcemia associated with administration of Na2EDTA. The case is under investigation by the Pennsylvania State Board of Medicine.

Alternative and augmentative communication and assistive devices/technology PECS is widely used and has been shown to be effective in some controlled trials, particularly when used in early childhood Speech generating devices: evidence for efficacy in minimally verbal children is emerging

PECS (Picture exchange communication System) There is consensus that PECS is likely to be beneficial in children who have little speech Useful video: Bzli1iC_w8https:// Bzli1iC_w8

Speech generating devices

Physical, speech, occupational therapy SLT is EFFECTIVE in increasing spontaneous speech, conversational competence, social communication OT is EFFECTIVE in improving gross and fine motor skills Sensory integration: empirical support is limited, but sensory integration approaches are often used in OT in children with atypical sensory processing

Behavioural and educational interventions

ABA substantial body of literature that supports the use of EIBI for children with ASD PRT Pivotal Response Training (focus on natural reinforcers) FloortimePlay-based, focuses on the child’s social-emotional development Early Start Denver ModelCombines elements from the above interventions TEACCHTeaching is based on the specific learning needs of children affected by ASD, including strength in visual processing

Early Intensive Behavioural Interventions Some RCT evidence Consensus based on clinical experience that EIBI are likely to be beneficial EIBI is a comprehensive form of intervention, based on the principles of Applied Behaviour Analysis, in which pre-school children are taught a wide range of skills by a specially trained group of therapists, normally including the parents of the children

TEACCH ( Treatment and education of autistic and related communication handicapped children ) Consensus that it is likely to be beneficial. RCT needed. ‘Is based on understanding the learning characteristics of individuals with autism and the use of visual supports to promote meaning and independence’

Comprehensive programmes targeting multiple core deficits ProgrammeEvidence of effectiveness Behavioural programmes based on ABAMODERATE Early Start Denver ModelMODERATE STARLOW Developmental programmesLOW TEACCHLOW ABA + TEACCHLOW

Psychosocial interventions PARENT MANAGEMENT TRAINING: effective in improving parental management of problematic behaviours (aggression, non-compliance, self injury) CBT: effective in reducing comorbid psychiatric symptoms Family therapy: may be helpful in supporting the well-being of the family

Social skills training Social expectations are clearly explained, modelled, practiced, and reinforced May be helpful, especially for high functioning or moderately affected children. Social skills groups for school-aged children with ASD have demonstrated enough evidence to be considered “an established Empirically Based Treatment” (EBT) Useful link: ls_training_groups_powerpoint.pdf ls_training_groups_powerpoint.pdf

Social skills training

Conclusions EIBI programmes are the treatment of choice and have been shown to improve outcomes significantly. The greatest strength of evidence for treatment of core social communication impairments exists for behavioural interventions, particularly when implemented early in development Use of psychotropic medications has a limited evidence basis, variable efficacy, and high rate of side effects, a careful medical evaluation is needed to rule out physical discomfort before starting medication

Research Novel treatments that target specific neurobiological processes in ASD and are effective for core deficits are an important area of focus for future research

British perspective

Clinical Evidence: Autism Dr Jeremy Parr Clinical Senior Lecturer/Hon Consultant Telephone: +44 (0) Fax: +44 (0) Address: Sir James Spence Institute Royal Victoria Infirmary Newcastle Upon Tyne NE1 4LP United Kingdom Jeremy Parr, Clinical Evidence BMJ May 2009, updated Jan 2010

Early Bird Programme There are no published data showing that the programme leads to better outcomes, but many parents find the course educational and helpful ‘The programme aims to support parents, empowering and helping them facilitate their child's social communication and appropriate behaviour in their natural environment. It also helps parents to establish good practice in handling their child at an early age, so as to pre-empt the development of inappropriate behaviours’

More than words Consensus based on clinical experience that it is likely to be beneficial Programme for Parents of children ages 5 and under in the autism spectrum: Parents learn: How the child learns best and what motivates him to communicate Why the child behaves in certain ways, and what can be done to either increase or reduce those behaviours Tips for using pictures and print to help your child’s understanding

Not recommended Digestive enzymes Gluten and casein free diet Omega-3 fish oil Probiotics Vitamin A Vitamin B6 + Mg Vitamin C Melatonin (?)

Not recommended Secretin Memantine Immunoglobulins Chelation Note: Thiomersal is no longer used in any of the vaccines routinely given to babies and young children in the NHS childhood immunisation programmeNHS childhood immunisation programme

Autism is treatable Although there is no known cure for autism, it can be treated so that the symptoms are not disabling - A non-verbal child can gain the ability to communicate - A non-social child can gain interaction skills With treatment, children with autism are not cured but can overcome the disabling aspects of the condition.

Thank you! If a child cannot learn in the way we teach, we must teach in a way the child can learn - O. I. Lovaas