Sertraline May Reduce Psychogenic Nonepileptic Seizures

Fran Lowry

October 14, 2010

October 14, 2010 — Flexible doses of sertraline, up to a maximum dose of 200 mg, may reduce the rate of psychogenic nonepileptic seizures (PNES) by 50%, according to the results of a pilot randomized controlled trial (RCT).

The finding provides class II evidence of the feasibility for a pharmacologic intervention for PNES, W. Curt LaFrance, Jr., MD, MPH, from Rhode Island Hospital, Brown Medical School, Providence, and colleagues write in the September 28 issue of Neurology.

"In addition to their established efficacy for treating depression and anxiety, serotonin selective reuptake inhibitors (SSRIs) have shown promise in trials for conversion or somatoform disorders and some personality disorders," the study authors write. "These frequently occurring comorbidities in patients with PNES make SSRIs particularly attractive as a potential treatment for patients with PNES."

They hypothesized that treating the Axis I and II serotonergic-mediated symptoms of depression, anxiety, and impulsivity in patients with PNES would reduce the seizures and chose to test sertraline (Zoloft, Pfizer) in this regard because of its broad indications, approved by the US Food and Drug Administration, and because it is the SSRI with the fewest drug interactions.

Having few drug interactions is an advantage in patients who have seizures because they also use antiepileptic drugs, the study authors note.

In this double-blind pilot study, the study authors randomized subjects aged 18 to 65 years with video electroencephalography–confirmed PNES to 12 weeks of sertraline or placebo. Sertraline was given at a dose of 25 mg starting at day 15 of the study and then increased biweekly by 50 mg to a maximum of 200 mg daily, unless limited by side effects.

Thirty-eight subjects were enrolled and 26 (68%) completed the trial. The intent-to-treat analysis, performed in 33 subjects, showed that those assigned to the sertraline arm experienced a 45% reduction in mean biweekly seizure rates during the 12-week course of the intervention, from 22 to 12 (ratio, 0.55; 95% confidence interval [CI], 0.32 – 0.93; P = .03), whereas those randomized to placebo experienced an 8% increase in mean biweekly seizure rate, from 13 to 14 (ratio, 1.08; 95% CI, 0.65 – 1.77; P = .78).

The pilot study's main limitation is its small sample size, the study authors note.

"A full-scale RCT is needed to establish efficacy for a pharmacologic intervention for PNES," they write, adding that such a trial will need to adjust for potential dropouts.

Evidence to Support Large-Scale Study

In an interview with Medscape Medical News, Dr. LaFrance noted that the results from the trial were encouraging but emphasized that it was not powered to determine the efficacy of the SSRI for treatment of PNES. Rather, its purpose was to assess the feasibility of doing a larger trial.

"Given that there have also been positive studies using SSRIs to treat other conversion disorders, the findings provided evidence to justify a large-scale study," he said.

Although medications may be an adjunct, other interventions, such as psychotherapy, may be necessary or essential to address the underlying psychological triggers for the seizures, Dr. LaFrance added. To that end, he and his team are conducting a pilot trial of combined medication and psychotherapy.

Commenting on the study for Medscape Medical News, Shlomo Shinnar, MD, PhD, professor of neurology, pediatrics, and epidemiology and population health at Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, said, "This is a very interesting study, and the first to demonstrate the feasibility of a randomized clinical trial for psychogenic nonepileptic seizures and to provide preliminary evidence that drug therapy with drugs used for psychiatric illness may be helpful in this setting."

But, he added, "as the title notes, this is a pilot study and more definitive trials are needed before this treatment can be recommended as first-line therapy for the disorder."

Dr. Shinnar lauded Dr. LaFrance and his team for their efforts. "The authors should be congratulated on a pioneering first attempt at an RCT with medications for this common and difficult clinical problem."

Dr. LaFrance serves on the editorial boards of Epilepsia and Epilepsy & Behavior, receives royalties from the publication of the third edition of Gates and Rowan's Nonepileptic Seizures, receives research support from the National Institutes of Health, Rhode Island Hospital, the American Epilepsy Society, the Epilepsy Foundation, and the Siravo Foundation; and has acted as a legal expert for Healthcare Litigation Support. Dr. Shinnar has disclosed no relevant financial relationships.

Neurology. 2010;75:1166-1173.

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