Placebo Response in Drug Resistant Epilepsy

In the March 13 early online issue of the journal Epilepsy & Behavior, Dr. Schmidt and colleagues present an intriguing analysis assessing what factors are associated with a placebo response in patients who have drug resistant epilepsy. Placebo response is defined as those individuals who actually improve based on taking a pill, often in the context of clinical trials, that has no clinical purpose or benefit like sugar or salt yet a response is seen when compared to the actual drug we are testing. This comparison is the cornerstone of proving a drug’s effectiveness in the US. When the placebo rate in the control group is high it sets a higher bar for the medication being tested to have to surpass in order to show an effect. In this particular study, the researchers looked at the placebo response in 359 adult patients with drug resistant epilepsy in adults from three randomized placebo control trials of the drug lacosamide. At the end of the 12 week period in which the drug is maintained, 23% of these patients who were randomized to placebo—not the drug-- had at least 50% seizure reduction. Several factors were identified which helped to predict if a patient was likely to have a positive placebo effect.

• A higher age at study entry

• A history of seven or more prior lifetime antiepileptic drugs lowered the chance of achieving placebo response

• A baseline seizure frequency of greater than 10 seizures per month

• Prior epilepsy surgery lowered the likelihood of a placebo response

The investigators concluded that the age at exposure to placebo and age of diagnosis of epilepsy, the number of prior lifetime seizure drugs, baseline seizure frequency, and a history of epilepsy surgery impact the placebo response in adults with drug resistant epilepsy.

Why is the important?

This is a provocative and interesting study because placebo effects are of concern particularly when seizure drugs are being judged in clinical trials by the FDA. Understanding the placebo response is essential in order for newer drugs to make it to market if they are clinically helpful.