Abstract
Multicenter Pilot Treatment Trial for Psychogenic Nonepileptic Seizures: A Randomized Clinical Trial.
LaFrance WC Jr, Baird GL, Barry JJ, Blum AS, Webb AF, Keitner GI, Machan JT, Miller I, Szaflarski JP; for the NES Treatment Trial (NEST-T) Consortium. JAMA Psychiatry 2014;71(9):997–1005. doi:10.1001/jamapsychiatry.2014.817.
IMPORTANCE: There is a paucity of controlled treatment trials for the treatment of conversion disorder, seizures type, also known as psychogenic nonepileptic seizures (PNES). Psychogenic nonepileptic seizures, the most common conversion disorder, are as disabling as epilepsy and are not adequately addressed or treated by mental health clinicians. OBJECTIVE: To evaluate different PNES treatments compared with standard medical care (treatment as usual). DESIGN, SETTING, AND PARTICIPANTS: Pilot randomized clinical trial at 3 academic medical centers with mental health clinicians trained to administer psychotherapy or psychopharmacology to outpatients with PNES. Thirty-eight participants were randomized in a blocked schedule among 3 sites to 1 of 4 treatment arms and were followed up for 16 weeks between September 2008 and February 2012; 34 were included in the analysis. INTERVENTIONS: Medication (flexible-dose sertraline hydrochloride) only, cognitive behavioral therapy informed psychotherapy (CBT-ip) only, CBT-ip with medication (sertraline), or treatment as usual. MAIN OUTCOMES AND MEASURES: Seizure frequency was the primary outcome; psychosocial and functioning measures, including psychiatric symptoms, social interactions, quality of life, and global functioning, were secondary outcomes. Data were collected prospectively, weekly, and with baseline, week 2, midpoint (week 8), and exit (week 16) batteries. Within-group analyses for each arm were performed on primary (seizure frequency) and secondary outcomes from treatment-blinded raters using an intention-to-treat analysis. RESULTS: The psychotherapy (CBT-ip) arm showed a 51.4% seizure reduction (P = .01) and significant improvement from baseline in secondary measures including depression, anxiety, quality of life, and global functioning (P < .001). The combined arm (CBT-ip with sertraline) showed 59.3% seizure reduction (P = .008) and significant improvements in some secondary measures, including global functioning (P = .007). The sertraline-only arm did not show a reduction in seizures (P = .08). The treatment as usual group showed no significant seizure reduction or improvement in secondary outcome measures (P = .19). CONCLUSIONS AND RELEVANCE: This pilot randomized clinical trial for PNES revealed significant seizure reduction and improved comorbid symptoms and global functioning with CBT-ip for PNES without and with sertraline. There were no improvements in the sertraline-only or treatment-as-usual arms. This study supports the use of manualized psychotherapy for PNES and successful training of mental health clinicians in the treatment. Future studies could assess larger-scale intervention dissemination.
Commentary
Evidence-based treatments for psychogenic nonepileptic seizures (PNES) have significantly lagged behind treatments for other psychiatric disorders. There are likely multiple reasons for this but the major reasons are the overwhelming focus on diagnosis by neurologists, the lack of ownership by psychiatrists who are the ones charged with treatment, and the lack of collaboration between the two disciplines (1). There are likely other reasons for the lag in treatments though. Many patients with PNES have difficulty following recommendations or engaging in treatment, perpetuating a cycle in the search for a nonpsychiatric diagnosis. Even when PNES patients establish care with a psychiatrist, data suggest that psychiatrists do not believe the video-EEG diagnosis rendered in the epilepsy monitoring unit and rather reintroduce the idea of epileptic seizures (2). Clearly, the topic of treatment for PNES is complex and goes beyond not having enough evidence-based treatments available for patients. There is a lack of knowledge about how to engage patients in their own treatment, and a lack of providers sensitive to the fact that these patients suffer from a legitimate, disabling illness. Fortunately, the research efforts within the field of neuropsychiatry and the move toward integration of care for PNES has led to burgeoning interest among providers and a move toward randomized controlled trial design to uncover effective evidence-based treatments. A recent updated Cochrane review on psychologic treatments for PNES concluded that evidence was slim for any one particular therapy but that cognitive behavioral therapy (CBT) seems to recurrently come out as an effective option (3).
The current article by LaFrance and colleagues is a small, randomized, pilot study performed at three academic medical centers in the United States as part of the NES Treatment Trial (NEST-T) Consortium. There were four different treatment arms to which patients were randomized: CBT–informed psychotherapy (ip) alone, CBT-ip + sertraline, flexible-dose sertraline, and “treatment as usual (TAU),” which consisted of follow-up with the treating neurologist at the same treatment intervals. The primary outcome was event frequency, and the secondary outcomes were quality of life (QOL), global functioning, psychiatric symptoms (including depression, anxiety, impulsivity, dissociation), and social interactions. Raters were blinded to the treatment arm, though the clinicians who were involved in the treatment, were not blinded. While 81 subjects met criteria for the study, between refusals and dropouts, 34 participated in the four conditions. The CBT-ip showed 51.4% seizure reduction and significant improvement in several secondary outcome measures: depression, anxiety, QOL, and global functioning. CBT-ip plus sertraline showed a 59.3% seizure reduction and improvement in global functioning as a secondary outcome measure. Flexible-dosed sertraline alone and TAU did not show significant improvement in event frequency. In addition, baseline scores on some psychiatric measures (depression, anxiety, and some somatic symptom scores) differed between the groups (with a significant difference on multiple comparisons noted between the combined arm and the sertraline or TAU). This did not mediate change in event frequency however. The study was a within-subjects’ design and was not powered to find differences between the different treatment groups. Also, the number of participants was quite small and may have been biased toward those motivated to do better, limiting the generalizability of the study. A larger sample could have been powered to find differences between treatments and could have distributed patients more equally based on the severity of psychopathology. Nevertheless, the feasibility of the approach was shown and will likely be the basis for a larger study to find the most effective treatments for PNES. These types of trials for patients with PNES or other conversion disorders will continue to move the field forward.
There remain some very important issues in the area of PNES treatment. How can we get patients engaged in their mental health treatment, and away from repeatedly showing up in emergency departments to receive yet another new anticonvulsant prescription and further or even repeated testing (4)? How can we make sure that mental health providers know and care about treating PNES and do not refer the patients right back to neurologists? Last, how can we teach the new generation of neurologists and psychiatrists that patients with PNES are just as disabled as patients with epilepsy and are not able to control the episodes on their own, just as if they had epilepsy? Evidence also shows that a substantial proportion of patients continue to suffer from PNES years after being diagnosed, and possibly even after receiving adequate treatment (5). Are we prepared to offer long-term treatment, handle the chronicity of this condition, and go beyond a short-term intervention? It is clear that evidence needs to be obtained beyond the specific treatment and focused on an entire methodology of interacting with patients with PNES so that these patients feel accepted and cared for, not blamed for their illness. This type of approach goes beyond the usual evidence-based treatments. Once we have the armamentarium of treatments available, we must be able to get patients with PNES to access and engage with mental health professionals in a sustained fashion to affect long-term improvement (6).