Longer Seizure During Electroconvulsive Therapy Linked to Lower MDD Remission

A new study discovered a longer seizure duration during electroconvulsive therapy was linked to a greater likelihood of major depressive disorder (MDD) remission within 1 week.¹ Likewise, preventing a seizure during electroconvulsive therapy with an anticonvulsant medication was associated with a shorter seizure duration and lower MDD remission rates.

“To our knowledge, this cohort study is the largest yet supporting the association between seizure length and remission from MDD after [electroconvulsive therapy],” wrote investigators, led by Cecilia Gillving, MB, a faculty of Medicine and Health at the University Health Care Research Centre in Örebro University in Sweden. “Seizure duration appeared to be indicative of adequate treatment quality.”

Electroconvulsive therapy is used to treat MDD, yet not a lot is known about the link between seizure length and treatment outcome.

“It has been a long-held belief that short seizures may not be as clinically effective as longer ones, but there has been little empirical support for this clinical observation,” wrote James Luccarelli, MD, in his commentary paper.²

Thus, Gillving and colleagues aimed to explore the association between seizure duration, potential confounding variables, and the treatment outcome of electroconvulsive therapy.¹ The team conducted a population-based cohort study, leveraging electroconvulsive therapy data from the Swedish National Quality Register, and including patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019. Investigators only used the seizure duration from the first electroconvulsive therapy session for each patient in the analysis.

The primary outcome was remission, defined by a score of ≤ 10 points on the self-assessment version of the Montgomery-Åsberg Depression Rating Scale 1 week after electroconvulsive therapy. Investigators analyzed the data from March 2021 to May 2024, using a multivariable logistic regression analysis to calculate the odds of reaching remission for MDD among each seizure duration group. The team also evaluated the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate.

The study included 6998 patients with 60.4% female and a mean age of 55.2 years. In total, 39.3% (n = 2749) reached remission after electroconvulsive therapy. Patients with a seizure duration of 60 – 69 seconds had the greatest remission rates compared with patients who had seizures that lasted ≤ 20 seconds (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.63 – 2.88; P < .001). A seizure ≤ 20 seconds had the lowest remission rate of 27.2%.

“The findings provide evidence for the relative ineffectiveness of short (less than 20 seconds) initial seizures at relieving symptoms of depression,” Luccarelli wrote.²

Furthermore, investigators wrote greater electrical charges were found to be linked to greater MDD remission rates (adjusted OR [AOR], 1.15; 95% CI, 1.04 – 1.28; P = .005) and shorter seizure duration (P < .001).1

“…the association of higher electrical dose with shorter seizure duration and higher remission rates…highlight the underlying complexity of these associations and call for caution in interpreting the results,” the team wrote.

Additionally, thiopental was linked to longer seizure duration and lower remission rates, compared to propofol’s duration (P < .001) and remission (AOR, 0.87; 95% CI, 0.79 – 0.97; P = .02). In contrast, a greater anesthetic dose was linked to lower remission rates (AOR, 0.84; 95% CI, 0.76 – 0.94; P < .001). The analysis showed the anesthetic dose was linked to shorter seizure duration, but this was insignificant (P = .23).

Moreover, anticonvulsant medications, such as lamotrigine, were linked to a shorter seizure duration (P < .001) but lower MDD remission rates (adjusted OR, 0.67; 95% CI, 0.53 – 0.53; P < .001).

Investigators wrote how the findings were limited by only studying patients treated with unilateral electrode placement, making the results non-generalizable to those treated with bitemporal electrode placement.

“The most actionable finding for [electroconvulsive therapy] practitioners is the inverse association of benzodiazepines and anticonvulsants with [electroconvulsive therapy] effectiveness,” Luccarelli wrote.² “While prior studies have not found these medications to be associated with shorter initial seizures, in this large sample the use of either medication class was associated with lower odds of remission. Results of this study support the need to search for more sophisticated measures for assessing the quality of [electroconvulsive therapy]-induced seizures, as the results suggest that there is indeed a sign of treatment effectiveness to be found.”

References

1. ^{Gillving C, Ekman CJ, Hammar Å, et al. Seizure Duration and Electroconvulsive Therapy in Major Depressive Disorder. JAMA Netw Open. 2024;7(7):e2422738. Published 2024 Jul 1. doi:10.1001/jamanetworkopen.2024.22738}
2. ^{Luccarelli J. Unraveling the Importance of Seizure Duration in Electroconvulsive Therapy. JAMA Netw Open. 2024;7(7):e2422693. doi:10.1001/jamanetworkopen.2024.22693}