Research Fact Sheet ~ Valproic Acid
What is valproic acid?
Valproic acid is a drug used to prevent seizures in people with epilepsy. It has been approved in Canada for more than 25 years. It is also used for migraines and, in some cases, for depression.
Why did the scientists study valproic acid for retinitis pigmentosa (RP)?
Scientists at the University of Massachusetts Medical School were looking for molecules of a particular size and shape in their efforts to understand some kinds of RP. The valproic acid molecule fit their molecular criteria. Since valproic acid was already an approved drug, they decided to assess the records of 14 RP patients, who had taken it. This is not the typical way to test a new treatment. Usually a treatment is compared to a placebo to be sure it has more benefit than nothing at all. This must still be done.
What do we know about valproic acid’s effects on people with RP?
Very little. Of the RP patients assessed, only seven had usable data. These people had taken between 500-750 mg of valproic acid over a variable period of time of two and six months. Six of these people had autosomal dominant RP. The amount of vision these people had before taking the drug varied greatly.
Five out of the seven people involved in this study seemed to have some improvement in the size of their field of vision. The median improvement in field size was about 10% over this short time, but two people had more dramatic improvements. Three people also had improvements in how clearly they could see (visual acuity). These findings are exciting however variations in these tests are common for people with RP. This study had too few people to know whether the drug was responsible for these changes
Will there be further study of valproic acid?
Absolutely! A trial of valproic acid has been funded in the USA; it began enrolling people with autosomal dominant RP in November 2010. It is taking place in three US cities (Dallas, Salt Lake City and Worcester/Boston). The trial will include 90 people and will last about three years. People interested in enrolling in this trial can find contact information and more details here.
When complete, this trial may provide enough evidence for your doctor to advise you about using valproic acid, if you have autosomal dominant RP. If it is successful, it will also provide the evidence needed to have the drug approved for this use.
Will it work for people with all kinds of RP – regardless of the gene involved?
We simply don’t know. The Foundation Fighting Blindness in the United States is funding pre-clinical studies to look specifically at whether valproic acid might benefit people with other genetic forms of RP. If this work shows promise, they will expand the clinical trial to include additional groups. Even if this is a successful treatment for some people with RP, it will likely not benefit all genetic types.
Can it be prescribed now?
Valproic acid is approved in Canada for seizures, so your doctor could prescribe it now for off-label use. However with so little evidence of benefit for RP and no information about the longer term effects of its use, your doctor would have no basis for prescribing this drug or having you risk its side effects.
Does it have side effects?
Yes, like all drugs, valproic acid has side effects. The most common are stomach upset (vomit, nausea, diarrhoea), fatigue, and hair loss, especially when people first begin taking the drug. In rare cases, it can also cause liver or kidney damage. An RP dose will likely be lower than the dose used in epilepsy, so these effects may be less severe.
The use of valproic acid should be avoided in pregnancy, since there is an increased risk of birth defects, particularly neural tube defects, like spinal bifida. A recent statement by the American Food and Drug Adminstration also indicated that children born to mothers who used valproic acid during pregnancy had "lower cognitive test scores than children exposed to other anti-seizure medications during pregnancy."
Updated August 2011. This text has been reviewed by Dr. Elise Héon (SickKids, Toronto), Dr. Robert Koenekoop (Montreal Children’s Hospital) and Dr. Ian MacDonald (University of Alberta).