May 27, 2013

Valproic Acid: The Perils of Using Drugs Off-Label

Almost three years ago, scientists at the University of Massachusetts Medical School reported on a preliminary clinical trial of the epilepsy drug, valproic acid, as potential treatment for autosomal dominant retinitis pigmentosa (adRP). The trial was a brief four-month snap-shot of the treatment of 7 people, but its findings were exciting. In five out of seven treated individuals, the visual field got larger. That study prompted a larger, more substantial and meaningful trial for people with autosomal dominant RP, and it, too, created a lot of excitement.

This drug was already available as a treatment for epilepsy, so people started to ask their doctors about how they could get it. In some cases, drugs can be prescribed off-label (i.e., used for conditions that they have not been approved for.)

Off-label drug treatment is tempting when positive research news suggests a promising treatment, but a recent research study has shown that it may not help us learn anything more about the treatment—and often it doesn’t help the people who chose to try it. Most doctors and scientists advised their patients against experimenting with valproic acid, when so little was known about its effects; however, a paper in the British Journal of Ophthalmology looked at the experiences of 31 people whose clinician agreed to prescribe the drug.

This evaluation was done after the fact; that is, the people taking the drug hadn’t planned to be in a trial and didn’t necessarily have regular testing done. From the data collected, the investigators could not see that the people involved had had any improvements in their vision. In fact, the only clear result in the data they could gather was a small decline in visual acuity (clarity of vision) amongst those people who had had visual acuity tests before and after beginning treatment.

Not only was there no evidence of benefit, but 12 of 31 people reported negative side effects, which were severe enough for 9 of those 12 patients to stop taking the drug. Two of the 12 experienced early signs of liver toxicity. Weight gain, fatigue and stomach irritation were some of the other commonly noted problems.

Retinal degenerative diseases arise from many different causes. The people who tried this drug had a variety of conditions, including retinitis pigmentosa, Stargardt disease and several other retinal dystrophies. It is unclear how many had an autosomal dominant form of RP, as in the original study.

“We can’t expect that what works for one type or RP will work for another,” says Dr. Bill Stell, Expert Scientific Advisor for Fighting Blindness Canada. “These people exposed themselves to unpleasant side effects, with no reason to expect benefit but a real possibility of further damage.”

Different genetic types of retinitis pigmentosa damage a person’s vision in different ways.  Several scientists—including FBC-funded scientist Dr. Orson Moritz—have begun to produce laboratory results which suggested that valproic acid might benefit people with some types of RP, but might be harmful to others.

“We need the results of research, such as that being done by Dr. Moritz, to identify the groups of people for whom valproic acid might be worth testing,” says Dr. Stell, “and we need properly designed and controlled clinical trials in which people take treatments under carefully monitored circumstances to determine benefit. We are certainly hopeful that trials of valproic acid will show that it is beneficial for people with some types of autosomal dominant RP, but without research, we can’t know that.”