It has been estimated that nearly half of adult patients with epilepsy do not achieve seizure control with available drugs. Patients with poorly controlled epilepsy are often on multiple anticonvulsants, which can cause debilitating side effects such as drowsiness, blurred or double vision and imbalance. New research is exploring other possible therapies, such as omega fatty acids.

Dr. Edward Bromfield, Chief of the Division of Epilepsy and EEG Department of Neurology at Brigham and Women’s Hospital and Associate Professor of Neurology at Harvard Medical School, is currently leading a study on polysaturated fatty acids (PUFA) for the treatment of refractory epilepsy. Dr. Bromfield is leading the study along with colleague Barbara Dworetzky, M.D. The following is an interview with Dr. Bromfield conducted by epilepsy.com editor Jenna Martin on the topic of fatty acids and epilepsy.

Q. “In previous studies geared towards the understanding of the role of omega fatty acids and refractory epilepsy, such as the one conducted by Rabinovitz, Mostovsky and Yehuda (1), an animal model was used. What are the implications of this study using an animal model as they relate to humans with epilepsy?”

A. “This study showed that a fatty acid preparation (one that includes both omega-3 and omega-6 fatty acids) was as effective as carbamazepine in a chemical convulsant model, and the fatty acids had fewer negative behavioral effects. Like previous encouraging results from animal studies, this makes us even more eager to determine how effective these compounds can be in human epilepsy.”

Q. “What are the long-term effects of using a fatty acid preparation (SR-3) in place of anticonvulsant medications like carbamazepine?”

A. “From what we know of PUFAs, particularly omega-3s, the long-term effects seem favorable, at least on the cardiovascular, dermatologic, and musculoskeletal systems. We don’t really know the long-term effects of most of the anticonvulsant medications, particularly the newer ones. But, if we could reduce the doses needed of some of the anticonvulsant medications by adding omega-3’s as part of treatment, whatever long-term risks exist would likely be reduced."

Q. “In the study conducted by Schlanger, Schnitzky and Yam (2), five patients completed the study and in all of them, a marked reduction in both frequency and severity of the epileptic seizures was recorded. Were these five patients taking anticonvulsants in conjunction with the 5g of fatty acids they consumed at breakfast?”

A. “Yes, they were still on their medications.”

Q. “Have there been other studies conducted using the same methodology in a more longitudinal form?”

A. “Not that I’m aware of. This open-label, case series was the first to report results in humans.”

Q. “In the study you are conducting now, what type of model are you using?”

A. “We are using a traditional, add-on drug study model.”

Q. “How is the study designed?”

A. “We are administering a supplement, a standard mixture of eicosapentanoic acid (EPA)and docosahexanoic acid (DHA) totaling 2.2 grams vs. a placebo, which is mineral oil. The dose is a little lower than the Israeli report. The design is standard. There is a four-week baseline period, during which people chart their seizures. Next, there is a twelve-week treatment period, during which subjects receive either the supplement or the placebo. The treatment will be randomly determined, and neither we nor the patients know whether they are getting PUFA or mineral oil. After all the patients have completed the study, we will then compare the percent reduction in monthly seizure frequency during the 12-week treatment period to the four-week baseline period for both the omega-3 and placebo groups.”

Q. “When did you begin the study?”

A. “We received financial support from the CURE foundation www.cureepilepsy.org/research/ as of Jan 1 and began the study then.”

Q. “How are participants in this study selected?”

A. “Inclusion criteria are broad- anyone with refractory epilepsy, which we are defining as four or more seizures a month, is eligible to participate. However, so that we can accurately determine the effects of the omega-3s, we are enrolling only patients who do not anticipate changing their medications during the course of the study.”

Q. “What expectations, if any, do you have of the outcome from this study?”

A. “We hope that this study will tell us whether or not omega-3s have any activity against seizures in people with epilepsy. If there appears to be an effect, then we would like to do a larger multi-center trial.”

Q. “Is the study mainly focused on adults?”

A. “Actually, we are about to enroll children in the study with our colleague Elizabeth Thiele, M.D., Ph.D., who directs the pediatric epilepsy center at the Massachusetts General Hospital for Children in Boston. Besides directing the center, Dr. Thiele is an expert on the ketogenic diet, and there is some evidence that this diet may work partly by altering polyunsaturated fatty acid (PUFA) in the blood and brain.”

Q. “Are there other recent studies beside the ones already discussed that you feel are relevant to mention?”

A. “Dr. Thomas Henry, from Emory University in Atlanta, presented a study at the American Academy of Neurology meeting(3) in which he found lower levels of DHA in red blood cell membranes of patients with refractory epilepsy than in controls. This raised the possibility of an actual deficiency of omega-3s in these patients, possibly related to anticonvulsant drug use that could theoretically be reversed by supplementation with omega-3s.”

Q. “When do you suspect the results from your study will be available?”

A. “We are hoping to have results in less than a year.”

References

1. Rabinovitz S, Mostofsky DI, Yehuda S. Anticonvulsant efficiency, behavioral performance and cortisol levels: a comparison of carbamazepine (CBZ) and a fatty acid compound (SR-3). Psychoneuroendicronology 2004 Feb;29(2):113-24.

2. Schlanger S, Schnitzky M, Yam D. Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia 2002 Jan;43(1):103-4

3. Henry T. Reduced cell membrane concentration of docosahexaenoic acid in patients with refractory complex partial seizures. Neurology 2004;62(Suppl 5):A353.