AAAP Today

CANCER TREATMENT MIGHT BE "RE-PURPOSED" TO TREAT AUTISM

Reported by Lirio Sobrevinas-Covey, Ph.D.

Individuals diagnosed with autism spectrum disorder (ASD) have much higher rates of cancer- related gene mutations. In a study involving a genomic database analysis, investigators initially found that autistic individuals have markedly increased rates of DNA mutations in genes associated with the development of cancer. A later study by Darbro and colleagues confirmed that earlier finding and, additionally, found that autistic patients have lower rates of cancer. It appears that children and adults with ASD exhibit a protective effect against cancer; this effect also appears to affect both males and females, although diminishing with age.

The significance of this finding is that certain cancer therapies may be “re-purposed” to treat autism. A possible explanatory mechanism is the presence of certain common cellular pathways for the development of cancer and of autism. Drugs that target cancer pathways might prove to have therapeutic value for treating autism. Some early suggestive evidence already exists. In a study of mice, rapamycin, a drug found to have anti-tumor properties was also found to prevent the development of autism. A trial of rapamycin in humans to study the benefits of rapamycin for patients with autism is underway. This is an exciting research direction towards a treatment for a condition for which an effective drug has yet to be discovered.

Reference: Benjamin Darbro, et al, Autism linked to increase oncogene mutations but decreased cancer rate. 2016, PLOS One.

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IMPULSE CONTROL FINDINGS WITH ABILIFY

By Lirio Sobrevinas-Covey, Ph.D.

In a recent post on AAAP (May 1, 2016), I had cited research findings indicating the efficacy of risperidone (Risperdal) and aripirazole (Abilify) for reducing irritability and aggression in children and adolescents with autism (Fung LK et al, 2016). This conclusion was based on findings from 46 randomized clinical trials involving these drugs and other anti-psychotic medications showing significantly greater symptom improvement among those who received the drug than those who received the placebo (Fung LK, 2016). Only Risperdal and Ability have been approved by the FDA.

My post included the cautionary statement from the meta-analysis that – “Both risperidone and aripiprazole when compared with placebo showed higher rates of sedation, somonolence, weight gain, and extrapyramidal symptoms.”

Further adverse effects of Ability, although rare and not specifically cited in the meta-analysis, have resulted in warnings from the FDA regarding impulse control problems associated with the drug.

“The FDA has become aware of other compulsive behaviors associated with aripiprazole, such as compulsive eating, shopping, and sexual actions. These compulsive behaviors can affect anyone who is taking the medicine. As a result, FDA is adding new warning about all of these compulsive behaviors to the drug labels and the patient Medication Guidelines for all aripiprazole products.”

The FDA recommends that clinicians make their patients and caregivers aware of these impulse control risks, and that they should specifically ask patients about the emergence of new or increased urges while they are using Abilify. As also suggested in my May 1 post in AAAP Today, the FDA advises clinicians to consider reducing the dose or stopping the medication if such urges develop. Patients should not make these changes without consulting their prescribing physician.

Reference: Catherine Cassels, Psychiatry and Mental Health, May 3, 2016.

FINDINGS FROM A REVIEW: DRUG TREATMENT OF IRRITABILITY AND AGGRESSION IN AUTISM

By Lirio Sobrevinas-Covey, Ph.D.

Irritability and impulsive aggression are significant problems of many persons with autism spectrum disorder (ASD), causing major challenges to the persons themselves and their families. Behavioral interventions are the first line of treatment for these conditions. Also important is to ascertain and, treat as needed, the influence of comorbid medical or psychological conditions, such as unreported pain, stress, depression, or anxiety that may be underlying the dysfunctional emotions and behaviors. When the first line approaches do not provide improvement, pharmacological treatment may be considered.

A review and meta-analysis was conducted to test the efficacy and safety of drug treatments for reducing irritability and aggression in youth (aged 2 to 17 years). Forty-six randomized clinical trials that compared the active drug to placebo were included. The measured outcome was the reduction of the patients’ score from baseline to the end of treatment on a behavior checklist – the Aberrant Behavior Checklist-Irritability (ABC-I).

The strongest evidence of significant improvement was observed for risperidone (Risperdal) and aripiprazole (Abilify). These two medications have received approval by the US Federal Drug Administration for treating irritability and aggression in autistic youth. Two other compounds (valproate and N-acetylcysteine) also showed significant symptom reduction but less strongly than risperidone and aripriprazole.

Both risperidone and aripiprazole when compared with placebo showed higher rates of sedation, somonolence, weight gain, and extrapyramidal symptoms. Thus, patients treated with these medications should be monitored for the emergence of those and other adverse effects. Withdrawal of the drug or dose change could follow.

Considerations of efficacy (does it improve symptoms?) and safety (does it have adverse effects?) are necessary when selecting which drug to use in cases of severe irritability and aggression. Combining the drug treatment with behavioral interventions and programs delivered by therapeutic professionals, family and caregivers, is of further importance. Emotional regulation, experienced in moments or days, bestows much sought-after quality of life for the person with ASD and his/her family.

Reference: Fung LK, Mahajan R, Nozzolillo A et al. A Systematic Review and Meta-analysis. Pediatrics 2016; 137.