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Reversible cognitive impairment associated with a high free fraction but subtherapeutic total blood level of valproic acid due to hypoalbuminemia in a bipolar patient

Published online by Cambridge University Press:  23 March 2020

G. Dautzenberg ,
M. Nederlof ,
E. Heerdink  and
A. Beekman
G. Dautzenberg*
Affiliation:
Altrecht GGZ, Old Age Psychiatry, Utrecht, The Netherlands
M. Nederlof
Affiliation:
Utrecht University, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands
E. Heerdink
Affiliation:
Utrecht University, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands
A. Beekman
Affiliation:
VU University Medical Center, Department of Psychiatry, Amsterdam, The Netherlands
*
*Corresponding author.

Abstract

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Valproic acid (VPA) is widely used in the treatment of epilepsy and bipolar disorder. It is largely bound to serum proteins (80–95%) in particular albumin, with a saturable binding capacity. Under conditions of hypoalbuminemia, protein binding of VPA will decrease and its pharmacologically-active free fraction will rise, even to toxic levels while measuring subtherapeutic VPA total blood levels [1].

We present an elderly bipolar patient with (sub)clinical total levels of VPA and a high free fraction of VPA due to hypoalbuminemia (14–24 g/L) leading to severe reversible cognitive impairment.

VPA and the free fraction in particular, was the most likely cause of the cognitive impairment [2]. There was a time-correlation with increasing blood levels of total VPA (68 mg/L, reference 80–120 mg/L [3]), notably the free fraction (37.5 mg/L, reference 5–15 mg/L), and the intoxication.

For therapeutic drug monitoring in laboratories, generally, total VPA concentrations (free + protein-bound) are measured instead of free fractions, due to technical difficulties, a lack of established reference ranges [4] and (inter)national guidelines [5,6] not requiring it. This presentation and literature points out that it is clinically relevant to measure the free fraction [7,8], especially in patients with hypoalbuminemia [9–11] to prevent unnecessary side effects and toxicity.

We recommend measuring albumin during VPA use; particularly in patients with nephrotic syndrome, liver disease [12] or older adults [13–15]. Hypoalbuminemia demands a free fraction measurement.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
e-Poster viewing: anxiety disorders and somatoform disorders
Information
European Psychiatry , Volume 41 , Issue S1: Abstract of the 25th European Congress of Psychiatry , April 2017 , pp. S420
Copyright
Copyright © European Psychiatric Association 2017

References

Hermida 2005.Google Scholar
Naranjo 1981.Google Scholar
TDMhttp://tdm-monografie.org/monografie/valproinezuur.Google Scholar
Dasgupa 2002.Google Scholar
NICE or NvVP bipolar disorder guidelines.Google Scholar
Dols 2016.Google Scholar
Levy 1980.10.3817/0680044155CrossRefGoogle Scholar
Jager Roman 1982.Google Scholar
Haroldson 2000.Google Scholar
Maat de 2011.Google Scholar
Jansen 2012.Google Scholar
Dasgupta 2007.Google Scholar
Rej 2012.Google Scholar
Beyenburg 2007.Google Scholar
Kodama 2002.Google Scholar
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