A type of psychotherapy that combines cognitive behavioral approaches with elements targeting trauma and interpersonal skills reduces seizures and improves psychiatric symptoms such as depression and anxiety in patients with psychogenic nonepileptic seizure (PNES), a new pilot study suggests.
Adding the antidepressant sertraline to this psychotherapy intervention further reduces seizures and also improves some psychiatric and quality-of-life measures, although not as many as the targeted psychotherapy alone, the study showed.
"What I think this tells us is that psychotherapy, with or without the medication, is going to help the typical complex patient with psychogenic nonepileptic seizures," lead author W. Curt LaFrance Jr, MD, MPH, assistant professor, psychiatry and neurology, Brown University, and director, neuropsychiatry and behavioral neurology, Rhode Island Hospital, Providence, told Medscape Medical News.
The article was published online July 2 in JAMA Psychiatry.
PNES is a neurological disorder associated with "underlying psychological conflicts or stressors" that manifest in seizures, said Dr. LaFrance. Patients with this disorder, which is the most common conversion disorder, experience real seizures, complete with "shaking and passing out," but these seizures are not caused by epilepsy, as verified by video electroencephalograph (EEG) monitoring, he said. Antiepileptic drugs (AEDs) are not indicated for the treatment of PNES; in fact, they could worsen the condition.
The study included adult patients at 3 sites with video EEG-confirmed PNES and at least 1 seizure event in the prior month. The study intentionally included "all comers," given that comorbidities such as anxiety, depression, and posttraumatic stress disorder are "the rule" in the PNES population, said Dr. LaFrance.
Participants were randomly assigned to receive 1 of 4 interventions: cognitive behavioral therapy–informed psychotherapy (CBT-ip), flexible-dose sertraline, combined CBT-ip and sertraline, and standard care/treatment as usual (TAU).
CBT-ip takes traditional CBT approaches and incorporates other therapeutic approaches, including interpersonal skills (to help with communication), mindfulness (an increasingly popular psychotherapy that helps people with 'distress tolerance'), and psychodynamic elements (targeting trauma issues).
The CBT group received 12 weekly, 1-hour individual sessions with a trained therapist. Participants and therapists used a workbook that was developed for a previous open-label assessment and modified for the current study.
Researchers chose sertraline, a selective serotonin reuptake inhibitor, for the study because of its limited interactions with AEDs and its indications for use with many comorbidities that occur with PNES.
A previous survey of neurologists indicated that TAU for PNES patients includes tapering of AEDs, referral to a psychiatrist or mental health provider, and possibly psychotropic medication for anxiety or depression, along with routine follow-up. Patients in the TAU group of this current study were seen biweekly for assessments in the same manner as those in the other treatment group.
For the primary outcome of seizure frequency, patients, assisted by family members or observers, logged seizures every day and kept seizure calendars prospectively each week. These weekly logs were reviewed at each appointment and entered into the database.
Participants also completed self-reported assessments of depression, anxiety, impulsiveness, trauma, quality of life, and function. Clinicians rated function (Global Assessment of Functioning) and depression (Hamilton Depression Rating Scale), as well as other outcomes.
The study was not designed for between-group differences but, rather, changes during the study. The analysis of 34 patients found that at study end, those in the CBT-ip group reported 51.4% fewer total monthly seizures (P = .01), and those in the combined CBT-ip plus sertraline group reported 59.3% fewer total monthly seizures (P = .008).
Participants in the sertraline-alone group had 26.5% fewer seizures, but this was not statistically significant (P = .08). The TAU group also did not experience a significant change in the number of seizures (33.8% reduction; P = .19).
As for secondary outcomes, the CBT-ip group had significant improvements "across the board," including measures for depression, anxiety, quality of life, and global functioning, said Dr. LaFrance. Meanwhile, the combination group had significant improvements in 7 of the 12 measures, including global functioning.
As well as having improvements on more of the secondary measurements, the CBT-ip-alone group had "better P values," said Dr. LaFrance. "With such a small sample size, it was surprising that there was such a big effect."
With a larger sample size, the researchers might have been able to determine whether there is a subset of patients for whom the combination therapy might work best, commented Dr. LaFrance. For example, he said, it might have a more powerful effect in those with seizures and posttraumatic stress disorder or in those with comorbidity.
The TAU group had no significant improvement in secondary outcomes.
There were some baseline differences in secondary measures; for example, the CBT-ip with sertraline group and the TAU group differed in baseline anxiety (87.5% vs 100.0%), mood disorders (77.8% vs 57.1%), and somatic symptoms (37.5% vs 42.9%). However, these differences did not have a moderating influence on seizure count.
Researchers also looked at the traditional 50% or greater responder rate. They found that most patients in all 3 treatment groups reported a 50% or greater reduction in the number of seizures (CBT-ip, 55.6%; CBT-ip with sertraline, 66.7%; sertraline, 55.6%)
In addition, the authors looked at a seizure freedom metric and found a high likelihood of patients being seizure-free if they were placed in either of the 2 psychotherapy groups. The odds of achieving seizure freedom were 6.2 times greater for those receiving therapy relative to those not receiving it (P = .06)
Speculating on why the CBT-ip therapy works so well, Dr. LaFrance said, "it takes the best of all the different psychotherapy modalities" and applies them to the challenging population of PNES patients. "It equips them with more and more tools and skills, and this empowers them, so they can actually start to take control of their seizures rather than being controlled by the seizures."
Patients in the study said they appreciated the newly acquired coping skills, even if their seizures did not abate completely. They also commented on the positive effects on relationships and activities and on medication adverse effects.
Those in the CBT-ip group also reported significantly fewer visits to the emergency department during the trials compared with before the study.
The study was relatively small, was not double-blind, and was not an efficacy trial, but it provides the first level 1 data for PNES. "[T]o our knowledge, the only 2 pilot [randomized controlled trials] for PNES include a traditional CBT approach (level 3 data) or a pharmacologic approach (level 2 data)," the authors write.
Although PNES has been in the medical literature for centuries, there has not been an effective treatment for this condition, which is often improperly diagnosed. On average, there is a 7-year delay between the onset of seizures and the correct diagnosis, said Dr. LaFrance. During that time, patients are prescribed AEDs, and then even more AEDs when they do not respond, which can lead to toxicity. Patients also endure repeated neuroimaging studies.
The modified workbook used in the study is being published, and Dr. LaFrance is training neurologists, psychiatrists, psychologists, and other providers to deliver what he calls "patient-led, therapist-guided" therapy.
The researchers are collecting data on the study subjects at 8 and 12 months to look at the durability of the intervention, said Dr. LaFrance. He hopes these new data will be published within a year.
Commenting on the findings for Medscape Medical News, Kari Martin, MD, assistant professor of psychiatry at the Mayo Clinic in Scottsdale, Arizona, said "it's wonderful" that the study showed improvement in symptoms for patient treated with CBT alone or with sertraline.
"I would be interested to know how long the benefit was sustained following the termination of the intervention," she noted.
Dr. Martin noted that PNES is seen in up to a third of patients presenting to outpatient neurology clinics and that the revised Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, has included this diagnosis in the "functional neurologic symptoms" category. "The new diagnosis does little to clarify the etiology of the illness, but it removes some of the stigma associated with pejorative terms such as 'psychogenic' or 'nonepileptic,' " she said.
Many patients with PNES resist psychiatric interventions and are highly sensitive to being labeled as psychiatric patients. "They have often had difficult interactions with the medical community, where they have felt invalidated," said Dr. Martin, adding that these patients also have "alexithymia" (trouble recognizing their own emotions).
Dr. Martin believes that CBT/behavioral therapy can improve patients' understanding of the mind–body connection and their registration of emotion. "It can be difficult to engage patients in a discussion of stress-associated symptoms when they can't identify their stress in the first place."
Past research has shown that CBT has some benefit, although short-lived, for functional neurologic symptoms; antidepressants, too, have had mixed results, said Dr. Martin.
"For patients who have had PNES symptoms for over 5 years, most therapeutic interventions appear to be fairly ineffective. The optimal patient for CBT or antidepressant medication would be a patient with a relatively brief history of illness coupled with a willingness to engage in psychiatric treatment."
For his part, Selim Bendadis, MD, professor and director, Comprehensive Epilepsy Program, University of South Florida, Tampa, found the evidence for efficacy of CBT-ip "compelling."
"This type of efficacy data should motivate neurologists to strive for an earlier diagnosis, and perhaps more importantly, should motivate mental health professionals to offer more widespread treatment."
Dr. Bendadis noted that psychiatrists and psychologists "generally show little interest" in somatoform disorders. "As a result, patients with PNES currently find themselves abandoned in the middle."
This work was supported by the American Epilepsy Society and by the Research Infrastructure Award from the Epilepsy Foundation. Dr. LaFrance has served on the editorial boards of Epilepsia and Epilepsia & Behavior; receives royalties for the publication of Gates and Rowan's Nonepileptic Seizures, 3rd Edition (Cambridge University Press, 2010); has received research support from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, Rhode Island Hospital, the American Epilepsy Society, the Epilepsy Foundation and the Siravo Foundation; serves on the Epilepsy Foundation professional advisory board; has received honoraria for the American Academy of Neurology Annual Meeting Annual Course and the Japan Epilepsy Society; and has provided medicolegal expert testimony. One coauthor has received research support from GlaxoSmithKline, Forest Pharmaceuticals, and Cyberonics and grant support from the American Epilepsy Society and the Epilepsy Foundation. Another coauthor has served on an advisory board for UCB Pharma; serves on the editorial board of Epilepsy & Behavior and the Journal of Epileptology; serves as an associate editor of Restorative Neurology and Neuroscience; has received honoraria from the American Epilepsy Society and UCB Pharma; and has received research support from the American Academy of Neurology, Davis Phinney Foundation/Sunflower Revolution, UCB Pharma, National Institute of Neurological Disorders and Stroke/National Institutes of Health, US Food and Drug Administration, Epilepsy Foundation, and University of Alabama at Birmingham Physical Medicine and Rehabilitation Foundation. The other authors have disclosed no relevant financial relationships.
. Published online July 2, 2014.
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Cite this: Psychotherapy May Be Best Approach for Psychogenic Seizures - Medscape - Jul 03, 2014.