Donepezil hydrochloride: a double-blind study in autistic children

Chez, Michael G.; Buchanan, Thomas M.; Becker, Marina; Kessler, Jami; Aimonovitch, Mary; Mrazek, Susan

doi:10.1055/s-0035-1557175

Cited by 10 publications

(1 citation statement)

References 14 publications

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“…The most researched cholinergic drug in relation to the disorder is donepezil. Donepezil reportedly increased both receptive and expressive speech, but did not influence executive functioning or overall autistic behaviors when compared to placebo (Chez et al 2003;Handen et al 2011). One placebo-controlled galantamine study has been conducted which reports improvements in hyperactivity, irritability, eye-contact and inappropriate speech (Niederhofer et al 2002; also see Ghaleiha et al 2014 where galantamine was added to the existing prescribed medication).…”

Section: Cholinergic Agentsmentioning

confidence: 99%

Catecholaminergic and Cholinergic Neuromodulation in Autism Spectrum Disorder: A Comparison to Attention-Deficit Hyperactivity Disorder

Koevoet¹,

Deschamps²,

Kenemans³

2021

Preprint

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Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social impairments and restricted, repetitive behaviors. Treatment of ASD is notoriously difficult and might benefit from identification of underlying mechanisms that overlap with those disturbed in other developmental disorders, for which treatment options are more obvious. One example of the latter is attention-deficit hyperactivity disorder (ADHD), given the efficacy of especially stimulants in treatment of ADHD. Deficiencies in catecholaminergic systems (dopamine (DA)), norepinephrine (NE)) in ADHD are obvious targets for stimulant treatment. Recent findings suggest that abnormalities in catecholaminergic systems may also be a factor in at least a subgroup of ASD. In this review we scrutinize the evidence for catecholaminergic mechanisms underlying ASD symptoms, and also include in this analysis a third classic ascending arousing system, the acetylcholinergic (ACh) network. We complement this with a comprehensive review of DA-, NE-, and ACh-targeted interventions in ASD, and an exploratory search for potential treatment-response predictors (biomarkers) in ASD, genetically or otherwise. Based on this review and analysis we propose that 1) stimulant treatment may be a viable option for an ASD subcategory, possibly defined by genetic subtyping; 2) cerebellar dysfunction is pronounced for a relatively small ADHD subgroup but much more common in ASD and in both cases may point towards NE- or ACh-directed intervention; 3) deficiency of the cortical salience network is sizable in subgroups of both disorders, and biomarkers such as eye blink rate and pupillometric data may predict the efficacy of targeting this underlying deficiency via DA, NE, or ACh in both ASD and ADHD.

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