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Small Study Examines Potential Treatments to Help Reduce Psychogenic Nonepileptic Seizures

Talan, Jamie

doi: 10.1097/01.NT.0000388908.26987.33

Psychogenic nonepileptic seizures (PNES) are a growing problem for neurologists as studies show that up to 20 percent of the patients they see for epilepsy may in fact have non-epileptic seizures. Researchers are now trying to develop treatments that reduce these seizures, known in psychiatric literature as conversion disorders.

In a paper published Aug. 25 online ahead of print in Neurology, investigators reported evidence from a small trial that suggests that pharmacologic treatment could reduce seizures in these patients.

Neurologists seem to have a difficult time delivering the news that a patient probably has psychogenic epilepsy, said W. Curt LaFrance, MD, director of Neuropsychiatry and Behavioral Neurology at Rhode Island Hospital and assistant professor of psychiatry and neurology (research) in the departments of psychiatry and human behavior and of clinical neurosciences at Brown Medical School, who led the study.

Some neurologists describe having a difficult time delivering the news that a patient probably has PNES. Dr. LaFrance said: “In our center, with video-EEG confirmation, we tell patients that they have seizures, but that they are not epileptic; and that it is good news that there is no abnormal neuronal activity that we generally see in epilepsy. We don't have a pill to stop psychogenic nonepileptic seizures, but in trying to develop interventions we thought that we could go after the comorbidities, for which we do have very good treatments.”

Dr. LaFrance and his colleagues designed a pilot randomized control trial funded by the NINDS to test sertraline, a selective serotonin reuptake inhibitor (SSRI) commonly used for treating depression, with 38 patients who under video-EEG and history were diagnosed with psychogenic epilepsy. They were treated for 12 weeks with either a placebo pill or the antidepressant. During that time, they kept seizure calendars and symptom scales. Of the 38 patients, 26 (68 percent) completed the study and were used in the final analysis.

All participants agreed to a clinical interview to assess possible comorbid diagnoses, including personality disorders. Study participants had at least one co-morbid condition, such as depression, anxiety, a personality disorder or post-traumatic stress disorder, and most had more than one. And they could be taking an antidepressant and participating in psychotherapy. But investigators excluded people who were just beginning therapy.

In addition to the daily seizure schedule, family members were encouraged to collect information as well. A trained and blinded rater assessed the patient's symptoms and psychosocial functioning scales at the beginning and end of the study.

Given the small size of the pilot trial, the study was not powered to determine the efficacy of the SSRI for treatment of PNES. The purpose of the study was to assess the feasibility of conducting a larger trial.

The doctors delivered a flexible dose of the SSRI up to a maximum dose of 200 mg over the three-month course of the study. Sixteen of the 19 patients in the active treatment arm were treated at a dose of at least 100 mg. Ten of the patients received a maximum dose of 200 mg daily.

There were no significant differences in the seizure count comparisons between the two groups (p=0.29). But when they looked for differences within each of the two groups (medicated and placebo) they found a 45 percent decline in seizures over the three-month course of the study in those taking the medicine. The frequency of biweekly seizures went from 22.24 to 12.18 (p=0.03) for those taking the SSRI. The placebo group had an 8 percent increase in biweekly seizures, from 13.38 to 14.38 (p=0.78).

“The study was conducted to establish an effect size for a pharmacologic intervention,” said Dr. LaFrance and his colleagues, “and to demonstrate feasibility of conducting a future multi-center randomized control trial for psychogenic nonepileptic seizures.”

Dr. LaFrance acknowledged that the study is too small to assess other secondary measures between the two groups, including changes in depression, anxiety, impulsivity, somatic symptoms, quality of life, and psychosocial functioning.

“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. He and others agree that while an SSRI may provide some symptomatic benefit, it is likely that depression and anxiety are comorbid problems and not the root problem among these patients.



Dr. LaFrance emphasized, “While medications may be an adjunct, other interventions such as psychotherapy may be necessary or essential to address the underlying psychological triggers for the seizures.”

Patients with PNES have a complex psychiatric and neurologic makeup, he noted. A number of patients with psychogenic nonepileptic seizures can have abnormalities on neuroimaging and on neurological examination. Patients in the study also had at least one co-morbid condition, such as depression, anxiety, post-traumatic stress disorder, or a personality disorder, and most had more than one.

The researchers are now expanding their study to multiple sites and combined medication-psychotherapy in a follow-up pilot trial. In a 2009 paper in Epilepsy and Behavior, Dr. LaFrance and colleagues reported on the results of a pilot trial involving cognitive behavioral therapy with 21 patients; 11 of 17 completers had a complete cessation of their seizures.

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Jerzy Szaflarski, MD, PhD, an associate professor in the departments of neurology, psychiatry and behavioral neuroscience at the University of Cincinnati, said that psychogenic seizures are becoming more and more recognized in the neurological clinic. Many uncontrolled cases of epilepsy, he said, may in fact be psychogenic seizures. The patient is generally seen by neurologist and once a diagnosis of psychogenic seizures is suspected a referral to a psychiatrist is made.

“These patients are thought to be converting stress into a physical symptom,” said Dr. Szaflarski, who was not involved in the study. “Many patients are in complete denial.

“The antidepressants appear to be effective but not an answer to all of their problems,” he added. “There was a high drop out rate in the study. What is clear is that these patients need a lot of help.”

Orrin Devinsky, MD, director of the New York University Epilepsy Center and professor of neurology and psychiatry, said that while the trial of SSRIs may benefit patients, the underlying disorder is not the depression or the anxiety, and the conversion disorder is unlikely to be cured with only a medication.

While he thinks the results of this study are important and encouraging, he believes that a combination of treatment with medicine and cognitive behavior therapy may ultimately work best.

Dr. LaFrance agreed with that assessment, adding that pilot studies investigating the combination are now under way.

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Investigators reported evidence from a small trial that suggests that sertraline could potentially reduce seizures in patients with psychogenic nonepileptic seizures.

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LaFrance WC Jr., Keitner GI, Miller IW, et al. Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures. Neurology 2010; E-pub 2010 Aug. 25.
    LaFrance WC, Jr., Miller IW, Ryan CE, et al. Cognitive behavioral therapy for psychogenic nonepileptic seizures. Epilepsy Behav 2009;14(4):591-596.
      ©2010 American Academy of Neurology