Clinical Articles by Dr. James O’Hanlon

…Stunningly, a highly significant treatment effect emerged 6 months after treatment had ended. Receptive language skills of the group treated with donepezil plus choline had continued to improve over the ‘washout’ period, whereas those of the placebo group remained the same. However, expressive language skills remained at previous levels in both groups. The implication is that pharmacological treatment started a self-perpetuating process in the brain that eventually improved the children’s ability to at least understand verbal language if not to use it themselves. One wonders whether their improved receptive language will eventually lead to better expressive language.

…Anti-inflammatory drugs are targeted on the pathophysiology of ASD not on behavioral symptoms that occur as consequence.  Many of those symptoms are assumed to be caused or at least exacerbated by neuroinflammation. Thus, when a drug successfully reduces neuroinflammation, one would expect a global reduction in ASD symptoms. Pioglitazone appears to have done this in early trials.

…Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger and homicidal ideation and threats have been reported in patients taking FYCOMPA…FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening.

…It would be surprising if pharmaceutical companies were not already engaged in developing drugs that specifically inhibit NKCC1. The first to gain official approval for the treatment of autism would be the real breakthrough. In the meantime, there is bumetanide.

…GWP has submitted a New Drug Application to FDA for approval of Epidiolex marketing and prescription for seizure control in Dravet and Lennox-Gastaut syndromes. FDA’s decision is expected this year. GWP is not stopping there. Phase III trials of Epidiolex in Tuberous Sclerosis are underway and early results are promising. Phase II trials with Infantile Spasms have recently begun. The four epilepsies addressed by Epidiolex are very different with respect to etiology and clinical presentation. It would be surprising if the drug were shown to similarly effective in every trial.

…Guanfacine emerged as the most efficacious drug for managing hyperactivity in children with ASD. Yet almost as much attention was given for adjusting guanfacine doses as for methylphenidate to achieve a balance between efficacy and tolerability. Neither drug can be effectively used without careful medical monitoring and dose adjustment. In contrast, atomoxetine was the least efficacious though well tolerated across its pediatric dose range. It is important to note that the same order of efficacy does not apply to typically developing children with ADHD. For them, methylphenidate (or amphetamine) is recognized as most effective drug for reducing hyperactivity, atomoxetine less and guanfacine least of all. It seems the pathophysiological processes that cause hyperactivity in ASD and ADHD are different.

…Developments that followed publication of this study were also unprecedented. Within a month, two major clinical trials with SFN involving individuals with ASD were commissioned by Governmental agencies. The first will be conducted at Rutgers University to completely replicate the original suforaphane trial with a new group of participants. The second allows continuation of Zimmerman and Talalay’s research. Similar methods will be used at the University of Massachusetts for measuring the effects of SFN in children with ASD, aged 3-12y. Additionally, tests will be applied for defining the biological basis for any improvement in the children’s behavior and mental functions. The former is scheduled for completion in 2022 and the latter in 2019. The results of these studies and others undertaken in the interim may show SFN to be the first effective treatment for core symptoms of ASD. They may also show that this hope was unjustified.