Naltrexone plus Topiramate (in Rats)

Effects of naltrexone plus topiramate on ethanol self-administration and tyrosine hydroxylase gene expression changes.

Navarrete F, Rubio G, Manzanares J.

Addict Biol. 2013 Apr 9

I don't usually report animal research here but this study caught my attention.

Rats were given naltrexone (0.7 mg/kg) and/or topiramate (25 mg/kg). 

The authors note "naltrexone significantly reduced ethanol consumption and the motivation to drink during the different stages of the experiment, whereas the treatment with topiramate resulted in a much lower effect. Interestingly, the administration of naltrexone plus topiramate reduced ethanol consumption markedly compared with single-drug treatment".

I interpret this to mean that naltrexone helped some, topiramate just a little (sometimes statistically significant) but the combination was much better than naltrexone alone.

As both of these medications are used to help alcoholism in humans, it might be reasonable to add topiramate when a patient on naltrexone is not yet remaining sober (or vice versa). Epocrates does note an interaction between the two: "combo may increase risk of CNS depression, psychomotor impairment (additive effect)" although I could not find a PubMed reference.  Sedation can be a problem with topiramate. 

Using topiramate on top of naltrexone might require a more careful dose titration. Most studies of topiramate for alcohol dependence aimed for a dose of 300 mg daily, but this was limited by sedation. I found one open label study showing efficacy at lower dose of 75 mg daily.

Review by Jim Walsh, MD