Weight change, genetics and antiepileptic drugs

Abstract

Weight gain caused by antiepileptic drugs (AEDs) constitutes a serious problem in the management of people with epilepsy. AEDs associated with weight gain include sodium valproate, pregabalin and vigabatrin. Excessive weight gain can lead to non-compliance with treatment and to an exacerbation of obesity-related conditions. The mechanisms by which AEDs cause weight gain are not fully understood. It is likely that weight change induced by some AEDs has a genetic underpinning, and recent developments in DNA sequencing technology should speed the understanding, prediction and thus prevention of serious weight change associated with AEDs. This review focuses on the biology of obesity in the context of AEDs. Future directions in the investigations of the mechanism of weight change associated with these drugs and the use of such knowledge in tailoring the treatment of specific patient groups are explored.

Keywords::

• epilepsy
• genetics
• obesity
• pregabalin
• sequencing
• valproate
• vigabatrin
• weight

Financial & competing interests disclosure

GL Cavalleri and N Delanty have received research funding from UCB Pharma. N Delanty has served on Advisory Boards for UCB Pharma, Eisai and GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Obesity is a common public health problem with long-term medical and psychological implications.

• Weight change is a common problem in patients with epilepsy, often due to treatment with antiepileptic drugs such as sodium valproate.

• Antiepileptics and antipsychotic treatments contribute to the rising prevalence of obesity. While most of these drugs cause weight gain, others cause weight loss while others are weight neutral.

• The biology of obesity is very complex and scientific knowledge in this area is rapidly evolving.

• Antiepileptic and antipsychotic medications interfere with the key biological mechanisms regulating energy balance. This might explain some of the weight-related adverse effects attributed to these medications.

• The development of gene sequencing technology has enhanced the understanding of the biology and genetics of obesity, and may also help us to understand antiepileptic drug-induced weight change.