Donepezil for Memory Enhancement in ECT

Out on PubMed, from researchers in India, is this study:Efficacy of donepezil for the attenuation of memory deficits associated with electroconvulsive therapy.

Dutta LCB, Sarkar CP, Andrade C.Psychiatry Res. 2020 Aug 18;293:113397. doi: 10.1016/j.psychres.2020.113397. Online ahead of print.PMID: 32835925

The abstract is copied below:

We sought to confirm and extend the findings of studies that reported that acetylcholinesterase inhibitor drugs protect against electroconvulsive therapy (ECT)-induced cognitive impairment. We randomized 30 patients with depression (n=24) or schizophrenia (n=6) to receive either donepezil (10 mg/day; n=15) or placebo (n=15) during a fixed course of 6 thrice-weekly, modified, bifrontotemporal sine wave ECT, and for 30 days subsequently. We assessed memory using the Postgraduate Institute Memory Scale (PGI-MS) at baseline, and again at days 2, 7, and 30 after the ECT course. At baseline, memory functioning was comparable in the 2 groups. At 2 days post-ECT, memory functioning was impaired on almost all 10 subtests and on the total scale. At 30 days post-ECT, memory functioning improved to (numerically) above baseline levels on almost all subtests and on the total scale, with the bulk of the improvement evident by day 7, itself. There was no significant difference between groups in the primary outcome, improvement in PGI-MS scores between Days 2 and 30 post-ECT. On almost all subtests, also, there was no significant difference between groups. In summary, we found that donepezil (10 mg/day) did not improve memory outcomes after ECT.

Keywords: Amnesia; Cognition; Donepezil; Electroconvulsive therapy; Memory.

And from the text:

"Neuropsychological functioning was assessed using the Postgraduate Institute Memory Scale (PGI-MS; Pershad and Wig, 1978). This battery, widely used in India, has 10 subtests, with a test-retest reliability of 0.69 to 0.85 for the 10 subtests (Pershad and Wig, 1978). These subtests, with maximum score stated in parentheses, are described as remote memory (6), recent memory (5), mental balance (9), attention and concentration (15), delayed recall (10), immediate recall (12), similar pairs (5), dissimilar pairs (15), visual retention (13), and recognition (10). This instrument tests new learning in verbal and visual domains, but also assesses past memories. Episodic, semantic, and working memory are all assessed. A total scale score (maximum, 100) is calculated."

The pdf is here.

This study is very well presented, including a discussion of its significant limitations. It was conducted in 2009-10, included only 30 patients (with diagnoses of either depression or schizophrenia) and used sine wave ECT. The use of the PGI-MS as the cognitive assessment battery, described above, is interesting, as it is not commonly used in ECT cognition research. 

The authors are very conservative in reporting their results, as there were actually hints of memory protection from donepezil, although very weak. The overall message, of the transient nature of ECT's memory effects, with one-month levels improved over pre-ECT baseline, is very encouraging.

I am hopeful that pharmacological enhancement of ECT may yet have a role in further improving the cognitive tolerability profile of the treatment. This is a line of research that has not been adequately pursued.