Epilepsycurrents.org
Current Literature
In Clinical Science
Issues in PNES Treatment
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 conver-sion 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 medica-tion (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, mid-point (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 mea-sures (
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 manual-ized psychotherapy for PNES and successful training of mental health clinicians in the treatment. Future studies could assess larger-scale intervention dissemination.
trists do not believe the video-EEG diagnosis rendered in the
Evidence-based treatments for psychogenic nonepileptic sei-
epilepsy monitoring unit and rather reintroduce the idea of
zures (PNES) have significantly lagged behind treatments for
epileptic seizures (2). Clearly, the topic of treatment for PNES is
other psychiatric disorders. There are likely multiple reasons
complex and goes beyond not having enough evidence-based
for this but the major reasons are the overwhelming focus on
treatments available for patients. There is a lack of knowledge
diagnosis by neurologists, the lack of ownership by psychia-
about how to engage patients in their own treatment, and
trists who are the ones charged with treatment, and the lack
a lack of providers sensitive to the fact that these patients
of collaboration between the two disciplines (1). There are
suffer from a legitimate, disabling illness. Fortunately, the
likely other reasons for the lag in treatments though. Many
research efforts within the field of neuropsychiatry and the
patients with PNES have difficulty following recommendations
move toward integration of care for PNES has led to burgeon-
or engaging in treatment, perpetuating a cycle in the search
ing interest among providers and a move toward randomized
for a nonpsychiatric diagnosis. Even when PNES patients
controlled trial design to uncover effective evidence-based
establish care with a psychiatrist, data suggest that psychia-
treatments. A recent updated Cochrane review on psychologic treatments for PNES concluded that evidence was slim for any
Epilepsy Currents, Vol. 15, No. 2 (March/April) 2015 pp. 68–69
one particular therapy but that cognitive behavioral therapy
American Epilepsy Society
(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
Issues in PNES Treatment
medical centers in the United States as part of the NES
and care about treating PNES and do not refer the patients
Treatment Trial (NEST-T) Consortium. There were four dif-
right back to neurologists? Last, how can we teach the new
ferent treatment arms to which patients were randomized:
generation of neurologists and psychiatrists that patients with
CBT–informed psychotherapy (ip) alone, CBT-ip + sertraline,
PNES are just as disabled as patients with epilepsy and are not
flexible-dose sertraline, and "treatment as usual (TAU)," which
able to control the episodes on their own, just as if they had
consisted of follow-up with the treating neurologist at the
epilepsy? Evidence also shows that a substantial proportion of
same treatment intervals. The primary outcome was event
patients continue to suffer from PNES years after being diag-
frequency, and the secondary outcomes were quality of life
nosed, and possibly even after receiving adequate treatment
(QOL), global functioning, psychiatric symptoms (including
(5). Are we prepared to offer long-term treatment, handle the
depression, anxiety, impulsivity, dissociation), and social in-
chronicity of this condition, and go beyond a short-term inter-
teractions. Raters were blinded to the treatment arm, though
vention? It is clear that evidence needs to be obtained beyond
the clinicians who were involved in the treatment, were not
the specific treatment and focused on an entire methodology
blinded. While 81 subjects met criteria for the study, between
of interacting with patients with PNES so that these patients
refusals and dropouts, 34 participated in the four conditions.
feel accepted and cared for, not blamed for their illness. This
The CBT-ip showed 51.4% seizure reduction and significant
type of approach goes beyond the usual evidence-based
improvement in several secondary outcome measures:
treatments. Once we have the armamentarium of treatments
depression, anxiety, QOL, and global functioning. CBT-ip plus
available, we must be able to get patients with PNES to access
sertraline showed a 59.3% seizure reduction and improve-
and engage with mental health professionals in a sustained
ment in global functioning as a secondary outcome measure.
fashion to affect long-term improvement (6).
Flexible-dosed sertraline alone and TAU did not show signifi-cant improvement in event frequency. In addition, baseline
by Barbara A. Dworetzky, MD
scores on some psychiatric measures (depression, anxiety, and some somatic symptom scores) differed between the
groups (with a significant difference on multiple comparisons
1. LaFrance WC, Devinsky O. The treatment of nonepileptic seizures:
noted between the combined arm and the sertraline or TAU).
Historical perspectives and future directions.
Epilepsia 2004;45(suppl
This did not mediate change in event frequency however.
The study was a within-subjects' design and was not powered
2. Harden C, Burgut FT, Kanner AM. The diagnostic significance of video
to find differences between the different treatment groups.
EEG findings on pseudoseizure patients differs between neurologists
Also, the number of participants was quite small and may
and psychiatrists.
Epilepsia 2003;44:453–456.
have been biased toward those motivated to do better, limit-
3. Martlew J, Pulman J, Marson AG. Psychological and behavioural
ing the generalizability of the study. A larger sample could
treatments for adults with nonepileptic attack disorder.
Cochrane
have been powered to find differences between treatments
Database Syst Rev 2014;Feb 11;2 :CD006370. doi: 10.1002/14651858.
and could have distributed patients more equally based on
the severity of psychopathology. Nevertheless, the feasibility
4. Smith B. Closing the major gap in PNES research: Finding a home for
of the approach was shown and will likely be the basis for a
a borderland disorder.
Epilepsy Curr 2014;14:63–67.
larger study to find the most effective treatments for PNES.
5. Duncan R, Graham C, Oto M, Russell A, McKernan L, Copstick S. Pri-
These types of trials for patients with PNES or other conver-
mary and secondary care attendance, anticonvulsant and antidepres-
sion disorders will continue to move the field forward.
sant use and psychiatric contact 5–10 years after diagnosis in 188
There remain some very important issues in the area of
patients with psychogenic non-epileptic seizures.
J Neurol Neurosurg
PNES treatment. How can we get patients engaged in their
Psychiatry 2014;Sep;85(9):954-8. doi: 10.1136/jnnp-2013-306671.
mental health treatment, and away from repeatedly showing
Epub
2014 Jan 20.
up in emergency departments to receive yet another new an-
6. Baslet G. Psychogenic nonepileptic seizures: A treatment review.
ticonvulsant prescription and further or even repeated testing
What have we learned since the beginning of the millennium?
Neu-
(4)? How can we make sure that mental health providers know
ropsychiatric Dis Treat 2012;8:585–598.
Source: http://www.epilepsycurrents.org/doi/pdf/10.5698/1535-7597-15.2.68
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