Sunday, 24 February 2013

Memantine and autism

As part of their review of autism research in 2012, the Simons Foundation Autism Research Initiative (shortened to the very catchy SFARI) had an interesting blogpost on all things drug development with autism spectrum disorders (ASD) in mind.

It was an interesting entry insofar as they had categorised the various medicines potentially indicated for some of the symptoms of ASD according to the stage of drug development including some formulations that have previously been fodder for this blog such as arbaclofen (see here), NAC (see here), minocycline (see here and here) and of course melatonin (see here). Without wishing to nit-pick, there was one important omission from the list - at least when I looked at it (29/12/12) - in the form of Dr Joan Fallon's CM-AT preparation which has also started making waves, but I'll put that to one side for now.

Tacuinum Sanitatis @ Wikipedia
Another compound which I've been hearing rumblings about for some time now was also included as a drug in phase II development.

The name: memantine, known under various trade names but with autism in mind, specifically Namenda by Forest Laboratories.

Searching through my blogpost archives I have made brief mention of memantine in a previous entry on some research looking at amyloid precursor protein in cases of autism. In that context, memantine was discussed with the management of symptoms related to Alzheimer's disease although touching upon the open-label study by Chez and colleagues* with autism in mind.

Given the very visible focus on glutamate and autism (see my post on GABA for an overview) it was always likely that memantine would get a look in when it comes to autism and autistic-like conditions. Memantine, I am reliably informed, blocks the action of glutamate by binding to NMDA receptors. That and a few other potentially important modes of action including some effect on cholinergic activity which I've always thought to be a rather interesting area as per articles like this one from Elaine Perry and colleagues** (open-access) and some potential synapse formation effects*** (open-access). It's probably no surprise that memantine has also been tentatively suggested for quite a few more psychiatric-based conditions**** including depression and schizophrenia.

I am rather interested in memantine and its possible uses (and misuses) when talking about autism. A quick trawl of the available literature suggests that an awful lot more needs to be done on this medicine with autism in mind as per its inclusion in the very useful pharmacologic autism treatment review by Doyle & McDougle***** (open-access) and its proposed effects particularly on the social interactive side of autism. Indeed trials are on-going (see here). Not least to also bear in mind are the various contra-indications and side effects (see here) which as always need to be balanced against potential therapeutic gains as required by good medicines management.

We wait and see... And while waiting, let's do some jammin' with Bob.


* Chez MG. et al. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol. 2007; 22: 574-579.

** Perry EK. et al. Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain. Am J Psychiatry. 2001; 158: 1058-1066.

*** Wei H. et al. The therapeutic effect of memantine through the stimulation of synapse formation and dendritic spine maturation in autism and fragile X syndrome. PLoS ONE. 2012; 7: e36981.

**** Zdanys K. & Tampi RR. A systematic review of off-label uses of memantine for psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 1362-1374.

***** Doyle CA. & McDougle CJ. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan. Dialogues Clin Neurosci. 2012; 14: 263–279.

---------- Chez MG, Burton Q, Dowling T, Chang M, Khanna P, & Kramer C (2007). Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. Journal of child neurology, 22 (5), 574-9 PMID: 17690064