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

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).

Electric field strength induced by electroconvulsive therapy is associated with clinical outcome

“…Therefore, it could be that there is not much gained by increasing the stimulus amplitude (and thus the electric field) further. There have also been small studies indicating that low amplitude seizure therapy using 500 mA might be effective ( Youssef and Sidhom, 2017 , Youssef et al, 2019 ) A recent trial comparing various stimulus amplitudes (600 – 800 mA) did, however, find that 600 mA resulted in worse ECT-outcome relative to 700 and 800 mA ( Abbott et al, 2020 ). More studies are definitely needed in this area.…”

Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes

“…DKEFS Verbal Fluency Test is a valid measure of cognitive side-effects because it is sensitive to the detection of amplitude-mediated neurocognitive impairment [ 28 ] and has been associated with structural neuroplasticity [ 29 ]. Subjects blinded to treatment-arm assignment received clinical, cognitive, and imaging assessments Pre-ECT (v1, before ECT treatments), mid-ECT (v2, after the six ECT treatments), and post-ECT (v3, within one week of finishing all ECT series) [ 28 , 34 ]. If subjects were nonresponsive to the assigned ECT treatments, they then switched to bitemporal (BT) electrode placement with a brief (1.0 ms) pulse width for the remaining ECT series (Fig.…”

Double-Blinded Randomized Pilot Clinical Trial Comparing Cognitive Side Effects of Standard Ultra-Brief Right Unilateral ECT to 0.5 A Low Amplitude Seizure Therapy (LAP-ST)

“…The titration algorithm UB-RUL ECT and LAP-St as well as the mean of the parameters of titration in initial and subsequent sessions, and seizure duration are all presented in a prior publication [ 39 ]. The titration was done in strict execution of the a priori protocol in the method.…”

“…As mentioned, given the descriptive nature and clinical heterogeneity of this pilot trial of 0.5 A, and small sample size, the results are not definitive, and caution is advised. Thus, the results should be replicated in large clinical trials of LAP-ST at 0.5 A, with a longer follow-up period to show long-term effects of LAP-ST on cognition, depression, and suicidality [ 39 ]. This would add to the emerging literature [ 32 , 39 , 44 ] as a practical therapeutic alternative for TRD with less CSEs.…”

“…The subsequent treatments were then performed at six times of the determined ST at the initial session for both treatment conditions. Titration parameters for the first treatment and subsequent treatments were presented in a prior publication [ 39 ].…”