Cognitive and Behavioral Interventions in Patients With Epilepsy

Cognitive and Behavioral Interventions in Patients With Epilepsy

Deepti Anbarasan, MD

The Neurological Institute of New York, Columbia University Medical Center, New York, New York

This year's Special Interest Group meeting on psychobehavioral interventions in patients with epilepsy spotlighted therapeutic elements of three specific cognitive and behavioral interventions and their clinical evaluation. The three interventions—acceptance and commitment therapy; progressive muscle relaxation; and a home-based, self-managed cognitive-improvement program—varied in delivery mode from face-to-face therapy to use of cell phones and telephone sessions. Target outcome parameters included patient quality of life, seizure frequency, and cognitive dysfunction.

Deepti Anbarasan, MDThis year's Special Interest Group (SIG) meeting on Cognitive and Behavioral Interventions for Epilepsy focused on the therapeutic elements of three psychobehavioral interventions. Acceptance and commitment therapy (ACT) uses mindfulness and behavioral change to address patients' perceptions of being diagnosed with epilepsy; progressive muscle relaxation targets stress reduction; and Home-Based Self-Management and Cognitive Training Changes Lives (HOBSCOTCH) uses problem-solving and compensatory mechanisms to improve memory, cognition, and quality of life (QOL). Investigators studying these interventions assessed their efficacy, cost-effectiveness, and improvements in patient functioning and satisfaction with their QOL.

This SIG meeting was coordinated by Lauren Frey, MD; Rosa Michaelis, MD; Marcio SoteroDeMenezes, MD; Siegward Elsas, MD; and Steve Schachter, MD.

ACCEPTANCE AND COMMITMENT THERAPY
Based on a presentation by Markus Reuber, MD, PhD, FRCP, Professor of Clinical Neurology, University of Sheffield–Royal Hallamshire Hospital, Sheffield, England.

As described by Dr. Reuber, ACT for patients with epilepsy involves a bidirectional relationship between epilepsy and depression. In a population-based study, Tellez-Zenteno et al1 demonstrated an increased prevalence of psychiatric comorbidities (eg, depression, anxiety) in patients with epilepsy compared with those who did not have epilepsy. Additionally, epileptic seizures can increase the risk of depressive and anxiety symptoms. Thapar and colleagues2 used a validated stress scale that showed stress, anxiety, and depression to be significant predictors of self-reported seizure frequency. According to Suurmeijer et al,3 patients rated psychosocial factors such as "psychological distress," "loneliness," "adjustment and coping," and "stigma perception" as being more important to their perceived QOL than were such clinical factors as seizure onset and frequency and the side effects of antiepileptic drugs (AEDs).

Lundgren and coworkers4 described the effectiveness of a psychotherapeutic treatment based on the ACT modality for patients with epilepsy. Clinicians using this form of cognitive-behavioral therapy seek to increase psychological flexibility by using both acceptance and mindfulness strategies to help change behavior. This form of therapy has been useful in treating depression, anxiety, diabetes, chronic pain, and (possibly) drug-resistant epilepsy.5

ACT in Patients With Refractory Epilepsy
Dewhurst and colleagues6 conducted an uncontrolled, prospective study involving consecutive patients who were referred for outpatient psychological treatment due to emotional difficulties related to refractory epilepsy. One therapist administered an initial 1.5-hour assessment followed by 6–20 individual outpatient sessions, spaced 1–2 weeks apart and lasting 50 minutes each; therapy was supplemented with a workbook. At the time of referral, the conclusion of the outpatient sessions, and 6 months afterward, participants completed a battery of self-administered questionnaires, including the Short Form-12 (SF-12) version 2, Generalized Anxiety Disorder-7 (GAD-7), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Work and Social Adjustment Scale (WSAS), and Rosenberg Self-Esteem Scale (RSES).

In all, 60 patients completed the pre- and posttherapy questionnaires; 41 of these patients also completed the 6-month posttherapy questionnaires. The median age of the group was 40 years (range, 19–75 years), and 46 of the patients (76.7%) were female. At the time of enrollment, 57.1% of the patients described themselves as "economically inactive," meaning that they were either unemployed or retired. The median scores noted on the pretherapy questionnaires were above the cutoff points for depression and anxiety, indicating the presence of significant psychiatric symptoms.

Completion of the ACT module was associated with significant improvements in self-reported psychiatric symptoms. Table 1 compares the median scores of the main outcome measures at baseline (T0), posttherapy (T1), and follow-up (T2).6 The investigators noted significant improvements in anxiety and depression symptoms (as measured by the GAD-7 and NDDI-E), in work and social functioning (as measured by the WSAS score), and in patients' self-esteem (as measured by the RSES score). Improvements also were seen in most scales of the SF-12, although changes in the physical-functioning subscale and the physical-health summary scale were not significant. No significant differences were seen between outcome measures obtained in the immediate posttherapy period and 6 months posttherapy, indicating that the benefits of ACT therapy were sustainable for at least 6 months.

Table 1

Notably, the change in median seizure frequency with ACT treatment did not reach statistical significance, as about 39.5% of patients experienced less than 50% improvement or no change at all, and about 37.2% of patients experienced a greater than 50% reduction in seizure frequency. However, the study did not control for changes in AEDs, and seizure frequency was not a primary outcome.

Cost Effectiveness
This treatment was considered to be cost-effective based on quality-adjusted life year (QALY) gains and overall cost of the therapy. Specifically, the mean cost of treatment for one patient (approximately $718) was associated with a 0.08 QALY gain. Based on these measures, the cost/QALY amount associated with sustained improvement of symptoms for 6 months would be $18,016, whereas the amount associated with sustained benefits for 12 months would be $8,979. This intervention was relatively inexpensive and cost-effective, based on the United Kingdom National Institute for Health and Clinical Excellence's cost-effectiveness threshold.

This ACT-based psychotherapeutic intervention resulted in significant and sustainable effects on depression, anxiety, QOL, adjustment, and self-esteem and was relatively cost-effective. Future randomized, controlled trials may help to validate this program in patients with epilepsy and concomitant mood or anxiety issues.

PROGRESSIVE MUSCLE RELAXATION
Based on a presentation by Michael Privitera, MD, Professor of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Dr. Privitera discussed the importance of evaluating and treating stress in patients with epilepsy. Results of diary studies have indicated that patients with epilepsy who perceive stress have a higher probability of experiencing seizures during the next 24 hours.7 Patients who report having stress-precipitated seizures tend to have higher scores on anxiety tests and to find that stress-reduction methods improve seizure control.8 As such, interventions that target stress may be helpful in patients with epilepsy who report stress as a possible trigger.

Physiologically, stress activates the hypothalamic-pituitary-adrenal (HPA) axis and leads to proconvulsant glucocorticoid release.9 Additionally, seizure-induced activation of the HPA axis also can contribute to additional seizure susceptibility. O'Toole and colleagues9 demonstrated that using pilocarpine to induce seizures in mice increases circulating levels of corticosterone, and treatment with a corticotropin-releasing hormone antagonist can block seizure activation in this rodent model.

Stress Management Intervention for Living With Epilepsy (SMILE) Study
Polak and others10 described the results of a randomized, controlled, double-blind trial in which an integrative medicine approach, such as diaphragmatic breathing and progressive muscle relaxation (PMR), was used with seizure-prediction methods as part of the SMILE study. Patients were eligible for inclusion in the study if they experienced at least two seizures per month, identified stress as a seizure trigger, and were on a stable medication regimen.

For the entire 5 months of the study, all participants monitored their levels of stress and other seizure triggers multiple times per day using a smartphone. After the first 2 months, patients were randomly assigned to the active-treatment group, which employed slow diaphragmatic breathing and PMR twice daily, or a control group for the remainder of the study. To minimize the risk of unblinding, the control group received a similar sham treatment, in which patients were led through a series of movements in the morning and then were asked to write down activities of the previous day in the evening.

In all, 67 patients completed the study. The median seizure frequency was reduced by 29% in the active-treatment group (P = 0.006) and by 25% in the sham-treatment arm (P = 0.064); no significant difference between the active-treatment and sham-treatment arms was observed. When excluding data at month 5 and comparing data at months 1 and 2 to the data at months 3 and 4, there was a 33% seizure reduction in the active-treatment arm (P = 0.009) and an 18% reduction in the sham-treatment arm (P = 0.171); this difference was statistically significant.

Both the active-treatment group and the control group appeared to improve from baseline, even though the primary outcome of seizure reduction over 3 months did not attain statistical significance. Use of the smartphone diary to record mood, stress, and seizures may have reduced seizures without formal relaxation interventions; even sham treatment may have had some therapeutic benefits in terms of stress reduction. Similar interventions must be examined in more detail. The next portion of this study will include cognitive or mindfulness treatment as part of active treatment.

IMPROVING COGNITIVE IMPAIRMENTS
Based on a presentation by Barbara C. Jobst, MD, Professor of Neurology, Geisel School of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

As shown by McAuley et al,11 there are vast discrepancies between actual patients' concerns about living with epilepsy and practitioners' impressions of these concerns. Patients identified their top three concerns as unexpected seizures, issues related to driving, and memory problems. Practitioners predicted the importance of the first two issues, but they did not identify memory problems as a prominent concern for this patient population. These investigators emphasized that practitioners should be more mindful of addressing concerns about memory in patients with epilepsy.

Dr. Jobst described recent efforts to evaluate interventions intended to decrease memory impairments associated with epilepsy. In a small case series, Suthana and colleagues12 evaluated the ability of deep-brain stimulation of the hippocampus or the entorhinal cortex to improve memory performance in patients with epilepsy. Entorhinal stimulation enhanced memory of spatial information when applied during the learning task, but direct hippocampal stimulation was ineffective. Michael Kahan, MD, a member of the "Restoring Active Memory" program sponsored by the Defense Advanced Research Projects Agency (DARPA), currently is leading a multi-institutional prospective study to identify neurophysiologic biomarkers for successful memory encoding and retrieval and, ultimately, to develop an implantable neural monitoring and stimulation system to treat memory loss.

Treatment of affective symptoms may be important when considering methods to improve memory complaints. Subjective memory complaints have been associated with word-finding difficulties and depression. As such, efforts to address depression in patients with epilepsy by improving identification of depressive symptoms and access to psychiatric care may improve both subjective memory and mood.13 Another potential therapeutic consideration may be cognitive rehabilitation, which may be useful in terms of memory improvement on formal neuropsychological testing.14 However, these interventions do not appear to improve patients' subjective memory complaints. Moreover, such programs require extensive resources and patient compliance, including frequent clinic visits and personal engagement.

The HOBSCOTCH Program
The HOBSCOTCH program for patients with epilepsy and memory or cognitive symptoms was developed at the Dartmouth-Hitchcock Epilepsy Center. This behavioral program uses self-management and problem-solving therapy to improve memory. It consists of one in-person office visit at the beginning and end of the program, as well as six weekly telephone sessions with an assigned memory coach. During the eight 45- to 60-minute sessions, patients learn skills related to memory, epilepsy, organization, and social function. They then exercise and apply their problem-solving techniques in their own lives between sessions. Patients who enroll in the HOBSCOTCH Plus program supplement weekly sessions with additional device-based working memory training using the Brain Age program (Kyoto, Japan: Nintendo Co., Ltd.) on a Nintendo DS handheld gaming device.

A randomized, controlled study recently was conducted at the Dartmouth-Hitchcock Epilepsy Center to evaluate the effectiveness of the HOBSCOTCH intervention in patients with epilepsy.15 A total of 66 patients were enrolled, randomized, and assigned to one of three groups: a control group, a HOBSCOTCH group, and a HOBSCOTCH Plus group. Forty-five patients completed the study. Patients in the HOBSCOTCH and HOBSCOTCH Plus groups reported significant improvement in their overall QOL after treatment. Neuropsychological testing revealed that patients in these groups earned higher posttreatment memory scores due to significantly improved attention subscores. There were no significant changes in reported depressive symptoms. The detailed results of the study are summarized in Table 2.15

Table 2

Subjectively, patients found the memory tools and relaxation techniques taught in the HOBSCOTCH curriculum to be beneficial. Participants in the HOBSCOTCH Plus group had difficulty using the Nintendo DS device, which objectively offered no additional benefit.

The HOBSCOTCH program may be a helpful self-management intervention to consider for patients having difficulty coping with memory-related disability. This program does not have to be delivered by a specialized provider (such as a neuropsychologist), and a significant portion of the intervention can be delivered over the telephone. In fact, two in-person sessions may be accomplished virtually to enhance cost-effectiveness and compliance; this modification must be studied further, however. Behavioral interventions can be effective for cognitive impairment in epilepsy, and more validated, well-designed studies will help us to understand better the role of such programs in patients with epilepsy.

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Dr. Anbarasan is a Clinical Neurophysiology Fellow at The Neurological Institute of New York, Columbia University Medical Center, New York, New York.

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