In March 2011, there was a supplementary paper released updating the guidelines in New Zealand, for three pharmacological interventions for autism spectrum disorder (ASD). Those three interventions are aripiprazole, citalopram, and melatonin. This updates the 2008 government publication “New Zealand Autism Spectrum Disorder Guideline” (NZ ASD guideline), which includes the section on pharmacological interventions at 4.4 in the book. The book also contains a list of drugs used for ASD in appendix 9. (Both 4.4 and appendix 9 are accessible via the link above.)
The NZ ASD Guideline is a comprehensive book made for the reference of families, individuals, and professionals dealing with ASD. It is a particularly good resource that looks at the entire life of the autistic person. The New Zealand Guidelines Group (NZGG) is tasked with updating recommendations and information in that book. It has recently released three updates that have only just come to my attention: The one I will be discussing in this post about pharmacological interventions (March 2011); one about ABA (May 2010); and one about diagnostic instruments (April 2011). I intend to do summaries of the other two later, but because of particular personal interest, I’m starting by looking at the pharmacological update. This post aims to summarise that paper. It is not a commentary.
The paper begins by pointing out that the primary interventions for autism are educational and behavioural interventions, rather than pharmacological. The pharmacological interventions cannot cure autism, but they can help manage conditions associated with, or comorbid with, autism. It was considered that the recommendations about pharmacological interventions included in the 2008 NZ ASD Guideline, may have been affected by recently published evidence on three medications, so the paper reviews and updates those recommendations where required. The researchers involved with the paper looked at controlled studies and systematic reviews, and graded them on quality, quantity, consistency, applicability, and the clinical impact of the studies.
(1) Atypical antipsychotic aririprazole (also known as “Abilify” and “Abilify Discmelt”).
Antipsychotics target irritability, aggression, self-injurious behaviour and severe tantrums (details of those problems are expanded on at 2.1 in the paper). Side effects of atypical psychotics include: metabolic and endocrine adverse effects, particularly in children; significant weight gain; and sedation. The existing guideline included risperidone as effective for aggressive, irritable and self-injurious behaviour, and as potentially useful for addressing restricted interests and patterns of behaviour.
Aripiprazole has potential for better side effects, for example it doesn’t impact on cardiac function, and has less impact on metabolic parameters; less impact on weight and less significant changes in glucose, lipid metabolism and serum prolatin.
The guideline group looked at eight studies (six systematic reviews and two randomized controlled trials (if you have a look at 2.2 and 2.3 in the paper you can read details of those studies and their respective strengths). The studies showed aripiprazole to be helpful in 6-17 year olds with ASD, for irritability, global improvements, and quality of life. It is a well tolerated mediation.
Their summary is that aripiprazole might be a good option where risperidone has not been affective, or has had bad side effects.
(2) A selective serotonin reuptake inhibitor (SSRI) citalopram (known as Celexa, Arrow Citalopram, Celapram, Citalopram Rex, and Cipramil).
SSRIs can be used to treat obsessive compulsive disorder (OCD). Direct quote: “Repetitive behaviour can be a disruptive and troubling feature of ASD, and may involve stereotypic movements, inflexible routines, repetitive play, and perseverative speech. Interrupting such routines can lead to anxiety, protest, aggression, and self-injury.”
The evidence considered was as follows (again, a direct quote): “The review update identified preliminary open-label trials of the use of citalopram, for people with ASD, two good quality systematic reviews, and a high quality multi-centre, triple blinded study of 149 children and adolescents, potentially the largest randomized medication trial ever conducted in children with ASD.”
The Guideline Group’s summary is that the evidence suggests citalopram is not effective in treating children and young people with ASD, with moderate or greater repetitive behaviour, and is associated with a small increase in mild to moderately severe adverse events, including increased energy, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia and dry skin.
Their conclusion was to not currently recommend the use of citalopram when considering the benefits versus harm for children and young people with ASD. And to be careful using it for comorbid conditions (eg OCD and anxiety) due to adverse effects in this population.
(3) Melatonin (a hormone)
Up to 89% of children with ASD have sleep difficulties, particularly dyssomnias (difficulty falling asleep and frequent night-waking). The risk with sedatives is daytime sedation and sleep-related breathing problems, and behavioural problems.
The Guideline Group looked at four systematic reviews and one cross-over trial. They found good and consistent evidence for use for ASD, especially where behavioral strategies were not working. Side effects were minor and infrequent. The Group decided to strengthen their previous recommendation for the use of melatonin.
They noted that there is no consensus on dosage level, and urged caution with long-term use due to a lack of long-term investigations. Behavioural strategies around sleep (“sleep hygiene,” including looking at day-time activities and environmental factors) should be used in tandem with melatonin.
I want to finish this post by pointing out that I have absolutely no medical training. If you would like more information – about the report or the recommendations it contains – you must click-through on the links I have provided, and of course, if you are considering any of these treatments for yourself or your family, talk it through with your medical professional. The purpose of this post was just to help make the updated information accessible and available, particularly to New Zealanders who may not have otherwise known about these changes.