But CBT shows secondary outcome benefits, CODES trial shows

Cognitive behavioral therapy (CBT) added to standard medical care offered no statistically significant advantage over standard medical care alone in reducing monthly non-epileptic dissociative seizures, the pragmatic, randomized CODES trial found.

A number of secondary outcomes suggested potential benefit for adjunctive CBT, however.

At 12 months, the median number of monthly dissociative seizures — sudden, involuntary seizure-like attacks, also known as psychogenic non-epileptic seizures — among patients randomized to CBT plus standardized medical care was 4, compared with 7 among patients who received standard medical care alone (IRR 0.78, 95% CI 0.56-1.09; P=0.144), reported Laura Goldstein, PhD, of King’s College in London, England, and coauthors in Lancet Psychiatry.

While the study failed to meet its primary endpoint, “improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardized medical care when compared with standardized medical care alone,” Goldstein and colleagues noted.

“Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists,” they wrote. “Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach.”

In an accompanying editorial, David Perez, MD, of Harvard University called the study “an important and landmark event in this area of research.”

“It is necessary to question whether this large, well-conducted clinical trial with a negative primary outcome proves that CBT is not incrementally effective for the treatment of dissociative seizures,” Perez observed. “In my opinion, CBT remains an effective treatment for dissociative seizures.”

Dissociative seizures are classified as a conversion disorder in the DSM-5. They have been difficult to treat, but growing interest and unmet need have led to recent studies involving psychotherapy, with or without other treatments.

“In the U.K., no standardized care pathway exists for people with dissociative seizures,” Goldstein and colleagues pointed out. “Although psychological treatment has been considered the treatment of choice, the availability of such treatment is variable, despite guidance that when dissociative seizures are suspected, referral should be made to psychiatric or psychological services for evaluation and intervention.”

In this study, Goldstein and colleagues recruited patients with a history of dissociative seizures from U.K. epilepsy centers (comorbid epilepsy patients were included if seizure-free for 12 months). Following a 3-month observation period — to avoid recruiting patients whose dissociative seizures might remit after receiving a diagnosis — they randomized 182 patients who were able to complete seizure diaries and questionnaires to standard care alone and 186 to standard care with CBT. Outcomes were assessed at baseline, 6 months, and 12 months, and analysis was intention to treat.

Mean age was about 38; 72% were female, and 90% were white. About a third were employed or in school. The dissociative seizures type was judged hypokinetic in 36% and hyperkinetic in 64%. Antiepileptic medication was used by 21%, and 24% had a prior doctor-reported diagnosis of epilepsy. More than half (58%) had scores suggestive of maladaptive personality traits, and 69% had another DSM-IV diagnosis.

In nine of 16 secondary outcomes, CBT plus standard medical care showed clinical benefit compared with standard medical care alone. Encouraging results included reports of less bothersome dissociative seizures and longer period of dissociative seizures freedom in the previous 6 months in the CBT group.

The CBT group also reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale, less impairment in psychosocial functioning on the Work and Social Adjustment Scale, less overall psychological distress on the Clinical Outcomes in Routine Evaluation-10 scale and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale. This group had better patient-reported clinical improvement at 12 months, better clinician-reported clinical improvement at 12 months, and more satisfaction with treatment.

However, no significant differences were noted between the two groups in dissociative seizures severity, or the proportion of patients who had a more than 50% reduction from baseline dissociative seizures frequency. There also was no difference in Short Form survey–version 2 Physical Component or Mental Component summary scores, Generalized Anxiety Disorder-7 scale scores, or Patient Health Questionnaire-9 scale depression scores.

Over 12 months, the number of adverse events was similar between groups (31% in the combined care group and 29% in the standard care group). Most common in the combined group were psychological events including mood deterioration. In the standard treatment group, musculoskeletal events resulting from dissociative seizures activity were most common. No adverse events or serious adverse events were deemed to be associated with the CBT plus standardized medical care intervention by independent raters.

The study raises two questions, Perez noted. “The first question is whether seizure frequency should be the preferred primary outcome measure in clinical trials for dissociative seizures,” he wrote.

“The second and equally necessary question pertains to whether the research community should continue pursuing a one-size-fits-all type of design for clinical trials involving dissociative seizures, in light of the trial findings to date, and the well-established heterogeneity observed in this population,” he added.

Limitations included reliance on self-reporting. Both groups in this study were contacted frequently by researchers and were required to complete seizure diaries throughout the study, which might have acted as an intervention, Goldstein and coauthors noted. In addition, findings may apply only to a largely white, mostly female population.

  1. Cognitive behavioral therapy (CBT) added to standard medical care offered no statistically significant advantage over standard medical care alone in reducing non-epileptic dissociative seizures, the pragmatic, randomized CODES trial found.

  2. A number of secondary outcomes suggested potential benefit to CBT, including less bothersome dissociative seizures, fewer somatic symptoms, less psychological distress, and more satisfaction with treatment.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was funded by the National Institute for Health Research.

Goldstein declared no competing interests.

Perez received honoraria from Harvard Medical School, the American Academy of Neurology, the Movement Disorder Society, Toronto Western Hospital, and Newton-Wellesley Hospital for continuing medical education lectures in functional neurological disorder.

Cat ID: 34

Topic ID: 82,34,730,34,192,146,925