Stress reduction techniques appear to reduce seizure frequency in patients with medication-resistant epilepsy, new research shows.
Researchers randomly assigned adults with medication-resistant focal seizures to participate in one of two interventions: progressive muscle relaxation (PMR) with diaphragmatic breathing or focused attention with a movement component.
After 12 weeks, seizure frequency was reduced by roughly one quarter in both groups, although PMR was more effective than focused attention in reducing self-reported stress.
“We’ve been very excited about doing this research and about these findings, because epilepsy really needs new, novel interventions, and we’ve gotten a really good reception to this from both doctors and patients,” lead author, Sheryl Haut, MD, professor of neurology, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, New York, told Medscape Medical News.
“We know that stress exacerbates seizures, so we think that multiple forms of behavioral interventions, including stress reduction, can potentially be very beneficial to our patients,” she said.
The study was published online February 14 in Neurology.
First RCT
“Despite advances in pharmacotherapy, at least one-third of individuals with epilepsy continue to experience seizures,” the authors write.
This has led to an “increasing interest in behavioral interventions,” especially in medically refractory seizures, because “stress is a frequently reported seizure trigger or precipitant in persons with epilepsy,” they add.
Previous research suggests improved outcomes with a mindfulness-based approach or behavioral interventions, but these studies have been “limited by small sample sizes, inadequate control groups, and nonseizure primary outcomes.”
To fill this gap, the researchers performed the first double-blind, randomized controlled trial of a stress-reduction intervention in people with medication-resistant epilepsy.
The primary outcome was percentage reduction in seizure frequency per 28 days between baseline and treatment.
Secondary outcomes included stress reduction and stress–seizure interaction.
Participants (n = 66; 62% female; mean duration of epilepsy, 26 [standard deviation, 13.7] years) were required to be at least 18 years of age, have medication-resistant focal epilepsy, be receiving a stable antiepileptic drug regimen for at least the prior 30 days, and be able to maintain an e-diary independently.
They also had to have experienced four or more seizures during a 56-day baseline and be aware of all seizures, seizure precipitants, and premonitory features.
Participants were randomly assigned to one of the two behavioral techniques.
The first, PMR, involved diaphragmatic breathing and a 16–muscle group practice, in which each muscle set was tensed vigorously without straining for 5 to 10 seconds, and then released.
The focused attention intervention was considered to be the control. Participants practiced a series of movements matched to PMR, but without the systematic muscle relaxation. They also engaged in other attentional tasks, such as writing down activities of the previous day.
Both groups were informed that they would engage in one of two possible behavioral techniques to be practiced daily but were not informed about which was hypothesized to be the active intervention.
Participants received individual training with a psychologist, then practiced twice daily on their own, following an audio recording on their smartphone. On a day where they experienced signs of having a seizure soon, they were asked to practice the technique another time that day.
Six weeks after randomization, participants received an in-person refresher training.
At baseline and 12-week follow-up, participants completed an array of questionnaires to assess mood (eg, the Beck Depression Inventory-II, Generalized Anxiety Disorder-7, and Neurological Disorders Depression Inventory for Epilepsy).
The e-diary questionnaires contained multiple mood items, as well as information about seizures, premonitory features, sleep hours, medication adherence, menstrual cycle, and intercurrent illness.
“We had done some diary studies before this current study and found that increases in stress were reliably reported by many patients prior to their seizures,” Haut recounted.
“Although these studies do not prove that stress actually causes seizures, it made sense for us to go ahead and conduct a treatment trial addressing stress, which is why we designed this stress reduction study,” she said.
Both Interventions Beneficial
Most participants (86%) in the study reported that stress was a seizure precipitant.
Participants in the PMR group (n = 33) were slightly younger than those in the focused attention group (n = 34). Adherence to diary entries was high, and only 3 patients discontinued the study (1 in the PMR group and 2 in the focused attention group).
The change over time did not differ across treatment groups in any of the analyses.
Both groups experienced a similar overall percentage improvement in seizure counts (29% in the PMR group vs 25% in the focused attention group; P = .38).
Over the baseline period, seizure trajectories did not differ across treatment groups (P = .61), and the rate of change in seizures was also stable (P = .84).
Likewise, during the treatment phase, the rate of change in seizures was again similar (P = .76), with both groups showing a decrease in seizures over time (P < .0001).
When the researchers evaluated seizures according to a weekly and daily time basis, they obtained similar findings.
They also observed sustained seizure reduction in both groups through month 3, although an earlier, nonsignificant seizure reduction occurred in the PMR group.
At the beginning of the treatment phase, the PMR group had faster decreases in stress (ie, more negative instantaneous rates of change) (P < .05 for the first 40 days).
Nevertheless, the mean stress levels for the two treatment groups on any given day during the treatment phase never significantly differed (P > .05 for all treatment phase days), despite treatment differences in rate of change over time.
Most participants in both treatment groups reported that stress, as well as seizures, was reduced by treatment, with no difference between the groups
Haut acknowledged being surprised by the results.
“We were starting to get the feeling that patients were finding both inventions helpful during the study, although focused attention was not designed for relaxation and was our control group, with PMR being the treatment group,” she said.
“People were finding that the experience of writing down how they were feeling on a regular basis multiple times a day was apparently having some benefit for them,” she added.
She noted that the response both groups experienced “shows that there is the potential for different people to respond to different interventions.”
“Fruitful” Research Direction
Commenting on the study for Medscape Medical News, Kimford Meador, MD, professor of neurology, Stanford University, California, who was not involved in this research, said, “The topic is important and the study was well done, adding to the evidence we have regarding how important the aspect of stress is when treating epilepsy.”
When “people have stress and other psychological symptoms going on, it is hard to get seizures controlled, so if you can control those symptoms, you can also improve the seizures,” Meador said.
Also commenting on the study for Medscape Medical News, Steven Schachter, MD, professor of neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, who was not involved with the study, called the relationship between stress, anxiety, and seizures in people with epilepsy “a fruitful area for research.”
The authors “should be congratulated for their rigorous study design,” and their “interesting results suggest a clinical benefit for behavioral interventions and highlight the need for further studies,” Shachter said.
He added, “Ultimately, identifying the neuropsychological mediators of this effect could launch a new strategy for developing new pharmacological and device-based treatment for epilepsy.”
Haut stated that in future research, “we would like to integrate physiologic measurements so we can get a sense biologically of what it is that reduces seizures with these interventions.”
This study was supported by an unrestricted grant from the Shor Foundation for Epilepsy Research and an unrestricted grant from the Epilepsy Foundation. Haut serves on the editorial board of Epilepsy & Behavior; received unrestricted grant support from the Shor Foundation for Epilepsy Research; serves/served as consultant for Acorda, SIGA, Eisai, Otsuka, and Engage Pharmaceuticals; and received compensation for expert testimony for a legal proceeding, Pesce vs NYPD. The other authors’ disclosures are listed with the original study. Meador serves as a consultant for the Epilepsy Study Consortium and on the editorial boards of Epilepsy and Behavior, Journal of Clinical Neurophysiology, and Neurology. Meador has received travel, meeting, and accommodation compensation from UCB Inc and receives research support from the National Institute of Neurological Disorders and the Stroke and Patient-Centered Outcomes Research Institute. Schachter has received grant/research/clinical trial support from LivaNova PLC (vagus nerve stimulator).
Neurology. Published online February 14, 2018. Abstract
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