Review: Valproate and Neuroprotection


The article reviewed here is ‘Valproate and Neuroprotection Effects for Bipolar Disorder’ by Murad Atmaca. This is a brief review looking at the potential neuroprotective effects of Valproate in Bipolar Disorder (BPaD). There is no stated methodology for this review. The author considers the evidence for BPaD as a neurodegenerative process by focusing briefly on one study showing a reduction in glial cells in area 9. There is then a look at Proton Magnetic Resonance Spectroscopy imaging studies which allow visualisation of cell components (e.g. choline-containing compounds which are found in neurons and glial cells). Atmaca then focuses on one of these compounds – N-acetylsaspartate (which is found in neurons alone) and builds the argument for suggesting that this may not primarily be a proxy marker for neuronal structural integrity one of the assumptions made in the literature as there is a reversibility in lowered NAA levels. However in order to progress, a decision has to be made about what NAA does represent and Atmaca seems to settle on the conclusion that lowered levels of NAA are equivalent to a loss of neurons or related losses (e.g. loss of axonal function). Using this assumption, Atmaca then looks at some of the MRS research in BPaD and notes that in one study the ratio NAA/CHO was lower in controls compared to those on a combination of Quetiapine and Valproate. There is then further indirect evidence of a protective effect of valproate against excitoxicity. A number of cellular mechanisms are then considered – effectively Atmaca attempts to outline some possible pathways through which any such effects might occur before finishing with a look at some evidence of reduced brain volume reduction with Valproate. Although cellular mechanisms would be expected to form the basis for drug effects, the more convincing evidence for drug effects come from sufficiently powered longitudinal randomised-controlled trials preferably over a reasonably long time period. However, this paper is concise and Atmaca puts some pieces of the jigsaw puzzle together although time and further evidence will tell if these are the right pieces.


Atmaca M. Valproate and neuroprotective effects for bipolar disorder. International Review of Psychiatry. August 2009. 21(4). 410-413.


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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.


  1. it would be interesting to know:

    – are these neuroanatomical changes (eg cell reduction, etc) the cause or the effect of the disease?
    – do these neuroanatomical changes have clinical significance or they may be induced, but they don’t cause any problem?


  2. Review: Valproate and Neuroprotection « The Amazing World of … is a good blog post, I was wondering if I could use this blog on my website, I will link it back to your website though.


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