It is clear that both patients and clinicians have an increasing interest in exploring behavioral interventions for epilepsy. The observation that changes in stress and mood appear to be related to seizure occurrence has long been reported, typically as the most frequently endorsed seizure precipitant in both questionnaire and prospective studies [1,2]. Furthermore, the high rates of comorbid depression and anxiety and impairments in quality of life (QOL) lead naturally to the attempt to address these conditions behaviorally, at least in part [3▪▪,4].
In the setting of societal awareness and familiarity with such modalities as mindfulness and wellness programs, these techniques are being observed more and more frequently in the epilepsy literature. The term ‘behavioral intervention’ is broad and can be applied to many approaches currently in use in epilepsy. These treatments range from well-recognized psychobehavioral modalities which can be considered to encompass behavioral, cognitive behavioral, and mind-body treatments  to forms of expressive psychotherapies such as art and music therapy. The development and utilization of web-based or app-based management programs for the self-management of epilepsy may also be viewed in the category of behavioral treatments [6▪].
Although there is robust evidence that behavioral treatments improve multiple elements of QOL, comorbid mood disorders, and medication adherence in epilepsy, the overall level of evidence that behavioral treatments can improve seizure outcomes remains limited [7,8,9▪▪]. This relates in large part to the difficulty in conducting randomized clinical trials (RCTs) for behavioral interventions . Despite these limitations, there is a definite trend toward subjecting these modalities to examination in controlled studies.
Herein, we summarize the latest developments in behavioral interventions in epilepsy, attempting when possible to highlight outcomes targeted to reduction of seizure frequency, QOL, and psychiatric comorbidities. The review is arranged by treatment modality, although this is an artificial organization as there is significant overlap across these approaches, for example, the concept of self-management is itself a cognitive behavioral approach.
Psychobehavioral interventions are defined as interventions based on the ‘theory of psychotherapy,’ and can be considered to encompass behavioral, cognitive behavioral, and mind–body treatments . Many of these interventions have been examined in epilepsy; these studies have generally been small or noncontrolled studies. Given the increased general interest in these modalities and the robust supportive data, there has been significant progress toward studying these techniques in RCTs.
A 2017 Cochrane review examined RCTs and pseudo-RCTs of psychological studies in epilepsy [9▪▪]. Of 24 studies reviewed, none were included in the meta-analysis, among them are studies of cognitive behavioral therapy (CBT) [11–14], mindfulness [15▪], self-management , psychoeducational intervention [17,18], and depression intervention . The authors conclusion was that psychological and self-management interventions improved health-related QOL and emotional well-being in adults and adolescents with epilepsy (Fig. 1) [9▪▪]. These findings led to the recent recommendation by the International League Against Epilepsy Psychology Task Force that ‘psychological interventions should be incorporated into comprehensive epilepsy care’ [3▪▪].
Cognitive behavioral therapy
CBT examines the relationships between thoughts, emotions, and specific outcomes, training the practitioner to replace maladaptive thought patterns with healthier cognitive and behavioral responses . As above, multiple studies have demonstrated improvements in CBT for health-related QOL and comorbidity outcomes [9▪▪].
A recent review of cognitive and behavioral techniques for epilepsy highlighted that the data for improved seizure outcomes with CBT are limited [21▪▪]. The observation that CBT may reduce epileptiform activity supports this approach for seizure reduction, however . Supportive data are available for the Reiter/Andrews method, an approach which relies on the assumption that the emotional content of seizure precipitation can be amenable to CBT . Trigger control and aura interruption techniques are often included in this treatment, with promising results albeit typically in small and/or uncontrolled studies [24,25].
Other promising forms of CBT are acceptance and commitment therapy (ACT), discussed below as integrated with mindfulness, and motivational interviewing, a form of psychotherapy which assists the practitioner to move away from a state of uncertainty toward positive decision-making . Motivational interviewing improved epilepsy medication adherence in a large 2015 randomized trial . Motivational interviewing was also tested as part of the WebEase self-management program [27,28], demonstrating improvement in multiple modalities including self-efficacy and medication adherence. This technique has not been proven to reduce seizures [21▪▪].
As per the National Center for Complementary and Integrative Health, mind–body interventions are those practices that ‘employ a variety of techniques designed to facilitate the mind's capacity to affect bodily function and symptom,’ and include a large and diverse group of techniques . Although there is a robust history of smaller studies, there has been a paucity of larger and/or RCTs of these interventions in epilepsy until recently. Within the past 2 years, however, two psychobehavioral RCTs have been published with seizure frequency as either primary [30▪] or secondary [15▪] outcome.
Mindfulness training directs the practitioner to focus on present moment stimuli with nonjudgment and acceptance, toward mindful attentional control . In 2015, Tang et al.[15▪] reported the results of a mindfulness-based assessor blinded RCT. In the trial of 60 completed participants, 30 participants each were randomized into the mindfulness and social support (active) arm vs. social support only (attentional control) arm. Each group met four times, and participants in the mindfulness group were encouraged to practice 45 min per day.
Participants in both groups showed significant improvements in the Patient-Weighted Quality of Life In Epilepsy Inventory (QOLIE-31-P) scores, although more patients in the mindfulness group than the control group had clinically important improvements (36.6 vs. 13.3%). Both groups also showed improvements in mood scores on the Beck Anxiety Inventory and Beck Depression Inventory-II and improvements in verbal memory, with more clinically significant changes present in the mindfulness group.
Seizure control improved in both groups, with a reduction in mean seizure frequency from 9.83 at baseline to 5.90 (change −3.93, 95% confidence interval −5.79, +2.08) postintervention in the mindfulness group, and 9.00–7.33 (change −1.67, 95% confidence interval −3.03, −0.30) in the social support group. The results were statistically significant (P < 0.001) in the within-group analysis (pre and postintervention for each group), however, there was no significant difference in the amount of change seen between the two groups.
This well-designed study demonstrated a strong role for mindfulness and possibly similar modalities for improving QOL in epilepsy. The secondary outcomes including memory and seizure control also appear more robust in the mindfulness group. However, an important observation is that gains are present in the control group as well. Although this may represent the equivalent of a ‘placebo’ response, this may alternately represent a real effect from the control intervention, similar to the Stress Management for Living with Epilepsy (SMILE) study (below), underscoring the challenges in control arms of behavioral studies.
Another RCT of ‘distance delivery’ mindfulness examined the effect of a mindfulness protocol delivered via Web or phone to prevent major depressive disorder in epilepsy . The Project UPLIFT study, part of the Managing Epilepsy Well Network (below) randomized 128 participants into a controlled crossover study of mindfulness vs. treatment as usual. Distance delivery mindfulness significantly reduced major depressive disorder as well as depressive symptoms .
Project UPLIFT included elements of ACT, a psychobehavioral technique on the borderlands between CBT and mindfulness, which has undergone evaluation in epilepsy [33,34] including a recent uncontrolled study . ACT aims to train the practitioner to use acceptance and mindfulness techniques in concert with commitment to behavioral change strategies, toward increasing psychological flexibility [33,35]. This technique has been shown to reduce seizures and depression, either alone or in combination with other modalities such as mindfulness or yoga .
Progressive muscle relaxation
Progressive muscle relaxation (PMR) is a relaxation method in which each muscle set is tensed and relaxed for stress reduction . PMR was examined for epilepsy a few decades ago [37,38] and has reemerged as a treatment in many medical conditions. The SMILE study completed 64 participants with medication-resistant focal epilepsy who were randomized to two groups in a double blinded manner [30▪]. The active intervention involved twice daily diaphragmatic breathing and PMR consisting of the progressive relaxation of 16 muscles. The focused attention control program included matched muscle movements without systematic muscle relaxation and attentional practice such as writing down daily activities. The participants underwent two in-person training sessions, and maintained daily smartphone diaries. Participants practiced with an audio file on the smartphone. The primary outcome of the SMILE study was change in seizure frequency with respect to baseline over the 3-month study period.
The two interventions both showed reductions in seizure frequency as compared with baseline although the groups did not separate significantly from each other (PMR group: 29%; focused attention control group: 25%; P = 0.38). PMR showed superior reduction of self-reported stress (P < 0.05). (Fig. 2) [30▪].
As in the mindfulness RCT, both the active and the control group showed improvements beyond what would have been expected as a placebo effect, based on results from reported placebo rates in epilepsy clinical trials which range from 9.9 to 19.7% [30▪]. In addition to robust seizure improvements, the efficacy appeared to increase over time, especially in the attentional control group, which is not the typical pattern of placebo response. The authors suggest that the daily monitoring of mood may itself represent a form of mindfulness [30▪].
Yoga and meditation
Yoga has become an increasingly frequent component of complementary and alternative therapies in many disorders, including epilepsy. Yoga is practiced in numerous different forms, with varying levels of attention placed on its basic components: controlled breathing, posture, meditation, and targeted flow of consciousness. Regardless of its form, yoga teaches participants to respond to internal stimuli in a conscious way, which may be particularly useful for patients suffering from various neurologic diseases, including epilepsy [39,40].
Several studies have shown that yoga can have demonstrable physiologic effects. For instance, Sahaja yoga has been shown to produce alterations in galvanic skin resistance (GSR), blood lactate level, and urinary vinyl mandelic acid. These alterations may collectively indicate reduced stress following yoga practice . Additionally, Sahaja yoga has been observed to produce electroencephalography (EEG) changes in patients with epilepsy, with power spectral analysis showing a shift in frequencies from 0–8 Hz to 8–20 Hz . Such EEG changes may be because of the modulation of hypothalamic and endocrine effects on the limbic and sympathetic nervous systems .
In recent years, a limited, but growing, body of research has investigated the potential for seizure frequency reduction with yoga and other guided meditative practices. A 2017 Cochrane systematic review of two controlled, unblinded trials encompassing 50 total epilepsy patients showed a potential beneficial effect from yoga on control of seizures [43▪]. Results of the overall efficacy analysis showed that yoga treatment was superior to no intervention and postural exercises mimicking yoga. The mean effect size varied from 1.1 to 2.1 fewer seizures per month, with additional improvements seen in seizure duration and likelihood of achieving 50% seizure reduction over 6 months. However, the review's conclusions were limited by the small number of trials included, small number of participants studied, and lack of blinding . Other studies have also found decreases in seizure frequency, with 50% seizure reduction response rates ranging from 27 to 78%. Response rates tended to increase the longer participants engaged in yoga programs, with studied periods varying from 3 months to 1 year [44,45]. These studies were similarly limited by small sample sizes and the lack of blinding or randomization.
In addition to reduction in seizure frequency, yoga has long been shown to have mental health benefits among psychiatric patients, as discussed in a 2018 review . The high comorbidity of psychiatric disease among epilepsy patients is well established and opens an additional potential benefit for yoga therapy. Although few studies have investigated mental health benefits among epilepsy patients in particular, a small group of epilepsy patients participating in yoga programs has scored higher on certain measures of overall QOL .
Biofeedback comprises a set of techniques whereby the practitioner becomes aware of involuntary physiologic processes to manipulate them by conscious mental control. Neurofeedback is a form of biofeedback therapy which is based on self-modulation of features of the EEG by the practitioner .
A number of small studies have examined electrodermal or GSR-based biofeedback [48–50], including at least one randomized controlled single blinded study of GSR biofeedback vs. sham . These studies report robust and sustained seizure reduction, and the apparent recent increase in this investigation appears well merited.
Neurofeedback has been investigated for use in epilepsy since the 1970s [51,52]. Using neurofeedback, entrainment of specific EEG frequencies is believed to influence seizure control and behavioral parameters. Typically, participants are positively reinforced for the production of specific frequencies, most commonly entrainment of slow cortical potentials or higher frequencies such as the sensorimotor rhythm.
The currently available literature is well summarized in a recent review . No recent randomized controlled trials have been reported and these modalities still remain in limited recognition and use in standard epilepsy treatment. One recent follow-up study did demonstrate a sustained effect of slow cortical potential neurofeedback to reduce seizures 10 years after initial training , suggesting that neurofeedback may be an underutilized strategy for successful seizure control.
CREATIVE ARTS THERAPY
The National Coalition of Creative Arts Therapies Association recognizes six creative arts therapy modalities, including art therapy, dance therapy, drama therapy, music therapy, poetry therapy, and psychodrama. . Two of these modalities in particular, music and art therapy, have been recently evaluated in epilepsy.
The effects of music on patients with epilepsy are undergoing increasing research and therapeutic investigation. Studies have focused on what has become known as the ‘Mozart effect’ . Most studies have focused on Mozart's sonata for two pianos in D major K448, although other compositions and combinations of music have been studied as well. Playing Mozart has been shown to reduce seizures and produce various EEG changes, including the reduction of interictal epileptiform discharges . Interestingly, comparisons between Mozart and Beethoven have shown that the latter fails to produce the same EEG changes as the former .
The Mozart effect is thought to be because of an increase in parasympathetic tone that occurs while listening to music . Recently, therapeutic music has been shown to reduce seizure frequency in patients with drug-resistant epilepsy, especially pediatric patients and those with severe/profound intellectual disability [58–60]. There have been at least two case reports of patients who have recovered from refractory nonconvulsive status epilepticus following exposure to music therapy [61,62]. In addition to seizure reduction, one study reported decreased irritability, tearfulness, and aggression toward self and others, as well as improved daytime vigilance and nighttime sleep quality among children with drug-resistant epilepsy .
Although music therapy clearly requires additional investigation, its easy accessibility and virtually risk-free profile make it an appealing option for adjunctive complementary treatment in epilepsy.
Epilepsy has been depicted in various forms of art for centuries . Many artists with epilepsy have found vivid and imaginative ways to depict their unique experiences in the preictal, ictal, and postictal states . One artist's example paints a compelling picture of what it might be like to regain awareness after having suffered a seizure (Fig. 3) . These illustrations portray poignant and often emotionally charged depictions of the experiences of those with epilepsy, although there has been a paucity of research investigating whether art therapy can offer quantifiable health benefits for epilepsy patients. One group in Turkey evaluated 50 stroke and epilepsy patients using the Beck Hopelessness Scale before and after an intervention involving the use of clay to make artistic figures. Although all groups trended towards improvement in the Beck Hopelessness Scale, the epilepsy subgroup did not reach statistical significance .
Another small study examined the effect of a four-session art therapy focus group on attitudes toward illness among children and adolescents with epilepsy. Although study participants were uniformly positive about their experience, no difference was seen in the Childhood Attitude Toward Illness scale following the intervention .
Although art therapy may be subjectively therapeutic among select patients, additional research is needed to further investigate the utility of art therapy among patients with epilepsy.
Self-management, as defined by the Agency for Healthcare Research and Quality as the ‘the help given to people with chronic conditions that enables them to manage their health on a day-to-day basis’ . Self-management is an increasingly important patient-centered tool to improve outcomes in epilepsy .
The ‘Managing Epilepsy Well’ Network, established in 2007, has supported multiple programs geared to epilepsy self-management, including many of the studies discussed here. The use of web-based and mobile apps serve as important vehicles for delivery of these interventions, toward self-optimized seizure control and QOL. Multiple elements of self-management can be monitored using these apps, as recently reviewed (Fig. 4) [6▪].
Although a full review of self-management in epilepsy is outside of the scope of this review, special attention should be given to a number of recent studies. In a 2015 trial, 83 participants with epilepsy were randomized into a self-management program called program for active consumer engagement in self-management vs. usual care (program for active consumer engagement in self-management) . The self-management training was delivered by a psychologist and trained peer with epilepsy, in an 8-week group that met one evening per week for 75 min. Topics included epilepsy-related medical, psychosocial, cognitive, and self-management issues. Participants in the active arm showed significant improvements in the Epilepsy Self-Management Scale as well as multiple subscales of the QOLIE-31.
The 2016 HOBSCOTCH (home based self-management and cognitive training changes lives) study randomized 66 study participants into three arms to investigate the impact of a self-management intervention targeting cognitive dysfunction on QOL and cognition in adults with epilepsy . Study participants in the active arm showed improvements in QOLIE-31 and the attention domain of cognitive testing. These findings were found to be generalizable in the 2017 interim analysis of a replication study .
Most recently, the SMART ('Self-management for people with epilepsy and a history of negative health events’) study published in 2018 randomized 120 participants into an active arm of remotely delivered epilepsy self-management vs. waitlist control [70▪]. The intervention was developed with stakeholder participation. The self-management intervention was an initial in person group session followed by seven group format sessions delivered via the internet. Participants in the active arm had significantly fewer negative health events and improved scores on multiple QOL instruments. Seizure severity scores were not affected by the intervention [70▪].
These studies confirm an important role for epilepsy self-management programs. Seizure outcomes have generally not been reported and this remains an area of great interest.
A final word on self-management relates to the current expansion of wearable devices. These devices have introduced the ability of persons with epilepsy to self-monitor physiologic parameters possibly linked to seizure triggers. The full potential of these apps and devices is likely not yet realized, but holds great promise. A cautionary note is that optimally balancing the quality vs. quantity of this continuous stream of data poses a challenge.
The expansion of adjunctive behavioral options for the treatment of epilepsy is very promising. The current literature suggests that various behavioral therapies may be associated with fewer seizures, respite from common epilepsy comorbidities, and improvements in QOL measurements. Rigorous randomized blinded clinical trials are a few, and remain an important research need.
Behavioral therapies are likely underutilized in the epilepsy population. For motivated and interested patients, appropriately chosen behavioral therapies are a reasonable approach to adjunctive epilepsy treatment. As patient-centered approaches gain increasing recognition, it is imperative that the field of epilepsy continue to explore and encourage investigation into the wide array of potential behavioral interventions in epilepsy.
Financial support and sponsorship
M.P. receives research funding from NIH 2U01NS038455–11A1, Epilepsy Foundation, GW Pharmaceuticals, SK Life Science. He serves as a consultant for SK Life Science, GW/Greenwich, Astellas (DSMB).
S.R.H. serves on the editorial board of Epilepsy and Behavior; and received unrestricted grant support from the Shor Foundation for Epilepsy Research. She serves as a consultant for Acorda (DSMB), Otsuka, and Engage Pharmaceuticals.
Conflicts of interest
There are no conflicts of interest.
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