STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

Erickson, Craig A.; Veenstra‐VanderWeele, Jeremy; Melmed, Raun D.; McCracken, James T.; Ginsberg, Lawrence D.; Sikich, Linmarie; Scahill, Lawrence; Cherubini, Maryann; Zarevics, Peter; Walton–Bowen, Karen; Carpenter, Randall L.; Bear, Mark F.; Wang, Paul P.; King, Bryan H.

doi:10.1007/s10803-013-1963-z

Cited by 113 publications

(84 citation statements)

References 29 publications

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“…While there is clear evidence that disruption to E/I balance is implicated in ASD, the direction of any such imbalance is less clear. Crucially, this may be important in understanding the variability seen in response to clinical trials of drugs that attempt to modulate E/I balance in ASD (Erickson et al, 2014). The data reviewed here highlight the importance of ambitious future research, which will obtain data from a range of different methodologies from large samples of participants.…”

Section: Resultsmentioning

confidence: 95%

Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

2016

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The balance of neural excitation and inhibition (E/I balance) is often hypothesised to be altered in autism spectrum disorder (ASD). One widely held view is that excitation levels are elevated relative to inhibition in ASD. Understanding whether, and how, E/I balance may be altered in ASD is important given the recent interest in trialling pharmacological interventions for ASD which target inhibitory neurotransmitter function.Here we provide a critical review of evidence for E/I balance in ASD. We conclude that data from a number of domains provides support for alteration in excitation and inhibitory neurotransmission in ASD, but when considered collectively, the available literature provide little evidence to support claims for either a net increase in excitation or a net increase in inhibition. Strengths and limitations of available techniques are considered, and directions for future research discussed.3

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Section: Resultsmentioning

confidence: 95%

Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

2016

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“…These data therefore highlight the possibility of different neural profiles in ASC -between different sub-types of ASD and / or between different brain areas Crucially, this may be important in understanding the heterogeneity seen in response to clinical trials of drugs that attempt to modulate E:I balance in ASC (c.f. Erickson et al, 2014). …”

Section: Differences (See Dickinson Et Al 2014 For a Full Discussion)mentioning

confidence: 99%

Superior orientation discrimination and increased peak gamma frequency in autism spectrum conditions.

Dickinson¹,

Bruyns‐Haylett²,

Smith³

et al. 2016

Journal of Abnormal Psychology

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While perception is recognised as being atypical in individuals with autism spectrum conditions (ASC), the underlying mechanisms for such atypicality are unclear. Here we test the hypothesis that individuals with ASC will show enhanced orientation discrimination compared to neurotypical observers. This prediction is based both on anecdotal report of superior discriminatory skills in ASC and also on evidence in the auditory domain that some individuals with ASC have superior pitch discrimination. In order to establish whether atypical perception might be mediated by an imbalance in the ratio of neural excitation and inhibition (E:I ratio) we also measured peak gamma frequency which provides an indication of neural inhibition levels. Using a rigorous thresholding method we found that orientation discrimination thresholds for obliquely oriented stimuli were significantly lower in participants with ASC. Using EEG to measure the visually induced gamma band response we also found that peak gamma frequency was higher in participants with ASC, relative to a well-matched control group. These novel results suggest that neural inhibition may be increased in the occipital cortex of individuals with ASC. Implications for existing theories of an imbalance in the E:I ratio of ASC are discussed.

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“…Acamprosate appears to be effective on autistic symptoms: however, apart from one single blind randomized trial (Erickson et al 2014a), all the reviewed studies (Erickson et al 2011(Erickson et al , 2013 were open-label, a design which implies several bias (in particular it could not be ruled out the placebo effect). Clinical impression of improvement was the main outcome measure in all experiments.…”

Section: Discussionmentioning

confidence: 99%

“…mild nausea and reduced appetite). The more recent study (Erickson et al 2014a) recruited 12 patients with ASD in a singleblind placebo lead-in trial. Each patient received 2 weeks of placebo followed by 10 weeks of acamprosate.…”

Section: Acamprosatementioning

confidence: 99%

Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies

Brondino

Fusar-Poli

Panisi

et al. 2015

J Autism Dev Disord

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Autism spectrum disorders are an emerging health problem worldwide, but little is known about their pathogenesis. It has been hypothesized that autism may result from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways. Commonly used medications such as valproate, acamprosate, and arbaclofen may act on the GABAergic system and be a potential treatment for people with ASD. The present systematic review aimed at evaluating the state-of-the-art of clinical trials of GABA modulators in autism. To date there is insufficient evidence to suggest the use of these drugs in autistic subjects, even if data are promising. Of note, short-term use of all the reviewed medications appears to be safe. Future well designed trials are needed to elucidate these preliminary findings.

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STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

Cited by 113 publications

References 29 publications

Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

Superior orientation discrimination and increased peak gamma frequency in autism spectrum conditions.

Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies

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