Should We Be Concerned about Weight Gain with Pregabalin (Lyrica®) for Restless Legs Syndrome (RLS)?

Fri, 15 Aug 2025 22:31:00 +0000

Pregabalin (Lyrica®) is one of three medications in the class of seizure drugs known as alpha-2-delta ligands along with its cousins gabapentin (Neurontin®) and gabapentin enarcarbil (Horizant®) that are the consensus first-line drugs for the treatment of restless legs syndrome (RLS). @andyberkowskimd of ReLACS Health dissects the concerns about weight gain when it comes to taking pregabalin.

For background on pregabalin in the treatment of RLS, watch this video:
https://youtu.be/rGpzmFOQzSk

For more information on gabapentin and Horizant, this video explains the differences:
https://youtu.be/PPFw-W9unvw

Pregabalin has known side effects that can including dizziness or drowsiness, but weight gain is another important concern of RLS patients at ReLACS Health when discussing this treatment. Very little is known about how pregabalin causes weight gain. It could be increased appetite, negative effects on the body's metabolism, or even simply a gain in water weight. Regardless, the risks for some patients seem to be consistently present in studies, but the degree of the effect on those who have weight gain may also be small.

Much of the research on pregabalin is in those with epilepsy (seizure disorder) as this was one of the original uses for the drug.

As referenced in the video, here is a link to the Chen et al. (2015) with risk of weight gain from pregabalin in epilepsy of 8.4% in the studies reviewed:
https://www.epilepsybehavior.c....om/article/S1525-505

Cabrera et al. (2012) showed about 1/6 of patients had weight gain of grater 7% on pregabalin:
https://www.tandfonline.com/do....i/abs/10.1185/030079

This study from Poppen et al. on 77 veterans treated for 12-18 months for neuropathy with pregabalin with a weight gain of about 3 pounds:
https://www.ncbi.nlm.nih.gov/p....mc/articles/PMC82218

This systematic review by Panebianco et al. shows the risk is common but tends to increase with dose increases:
https://www.ncbi.nlm.nih.gov/p....mc/articles/PMC66149

This is important to those with RLS who may be taking 75-150 mg for RLS rather than as much as 600 mg/day for epilepsy.

Lastly, Hamandi et al. (2006) showed an average weight gain of 1-2 pounds and about 9% greater chance of weight gain over placebo in a few studies of pregabalin in epilepsy.

The bottom line is that weight gain is common but may not be severe. It also may not be bothersome at lower doses of pregabalin. As with all treatment interventions, one must weigh (pun intended) the risks of the unwanted effects with the treatment benefits. With increase in body mass from medications, small adjustments to lifestyle whether improved sleep, more exercise, reducing processed carbs and added sugars, etc. can go a long way to offsetting weight gain from pregabalin.

To read in more depth about RLS and other sleep disorders, follow A ReLACSing Blog:
https://www.relacshealth.com/blog

For those who live in or near Michigan, Ohio, or Florida, you can hire @andyberkowskimd as your own physician for advice on pregabalin, RLS, or any other aspect of sleep health. Go to https://www.relacshealth.com/ for more information.