Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial

Nagy A Youssef, Dheeraj Ravilla, Cherishma Patel, Mark Yassa, Ramses Sadek, Li Fang Zhang, Laryssa McCloud, William V McCall, Peter B Rosenquist, Nagy A Youssef, Dheeraj Ravilla, Cherishma Patel, Mark Yassa, Ramses Sadek, Li Fang Zhang, Laryssa McCloud, William V McCall, Peter B Rosenquist

Abstract

Background: Although treatment guidelines support use of electroconvulsive therapy (ECT) for acute suicidality, it is associated with cognitive side effects. The effect of Low Amplitude Seizure Therapy (LAP-ST) on suicidality is unknown. Our prior precision LAP-ST (pLAP-ST) performing titrating in the current domain has provided initial proof of concept data in humans of its advantage in terms of reduction of cognitive side effects. The aims of this report are to: 1) compare LAP-ST (at 500mA) versus standard Right Unilateral (RUL) ECT (at 900 mA) in terms of magnitude of remission of suicidality in a randomized allocation and 2) compare the speed of remission of suicidality between LAP-ST versus RUL ECT. Methods: Patients were randomized to either LAP-ST or RUL ECT. The scores pertaining to the suicidal ideation (SI) item on the Montgomery-Åsberg Depression Rating Scale (MADRS) were analyzed using descriptive analysis and no confirmatory statistical analysis was performed due to a priori sample size limitations for this pilot study. SI item remission was defined as 2 or below on this item. Results: Eleven patients with major depressive episode (MDE) of mainly unipolar or bipolar disorders signed consent. Of these, 7 were eligible and were randomized and included in the analysis; all were actively suicidal at baseline (suicide item above 2), except 1 patient who had suicide item at 2 in the RUL ECT group. Suicidality remitted on average by session 3 and remission occurred for all patients by session 4. The SI mean score improvement from baseline to endpoint for LAP-ST was 5.1 and for RUL ECT was 3.0. Conclusions: LAP-ST has larger effect size and speed of remission of suicidality compared to standard RUL ECT. Future studies are warranted for replicating these findings. (ClinicalTrials.gov ID: NCT02583490).

Keywords: Randomized Clinical Trial; electroconvulsive therapy; focal ECT; low amplitude seizure therapy; mood disorders; precision low amplitude seizure therapy; seizure therapy; treatment-resistant depression.

Conflict of interest statement

N.A.Y. receives research support from MECTA Corp and Merck, the Department of Veteran Affairs and The Augusta Biomedical Research Corporation. N.A.Y. received Speaker CME honoraria from the Georgia Department of Behavioral Health and Developmental Disabilities (DHBDD) and Psychiatric Annals for unrelated CME topics. W.V.M. receives research support from MECTA Corp and Merck, is a paid scientific advisor for Sage Therapeutics and receives royalties from Wolters Kluwer.

Figures

Figure 1
Figure 1
CONSORT Diagram.
Figure 2
Figure 2
Percentages of Unremitted Suicidal Ideation each Session for RUL ECT vs LAP-ST.
Figure 3
Figure 3
Means of suicidal ideation (SI) Item Score by Treatment Group in Each Session.
Figure 4
Figure 4
Suicidal Ideation Item Score of Average Change from Baseline at Each Session.

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