Use of Cholinesterase Inhibitors for Treatment and Prevention of Cognitive Adverse Effects of Electroconvulsive Therapy

Abstract Although electroconvulsive therapy (ECT) is effective for treating depression, schizophrenia, and mania, cognitive adverse effects may limit use. One possible mechanism for these effects includes cholinergic transmission alterations, supporting potential use of cholinesterase inhibitors for prevention and treatment of these cognitive deficits. The objective of this review is to determine efficacy and safety of cholinesterase inhibitors clinically used for dementia in reducing ECT cognitive adverse effects. PubMed, EMBASE, and CENTRAL were searched in August 2024 for randomized controlled trials using terms and keywords related to cholinesterase inhibitors ( acetylcholinesterase inhibitor , cholinesterase inhibitor , donepezil, galantamine , or rivastigmine ) and ECT ( electroconvulsive therapy , electroconvulsive , electroshock therapy , or ECT ). A total of 8 randomized controlled trials were reviewed with mean patient ages ranging from 28.6 to 59.33 years and most common diagnoses including depressive disorders, schizophrenia/psychosis, and bipolar disorder. Six of the 8 trials showed benefits of using cholinesterase inhibitors in patients undergoing ECT. Significant improvements were found in immediate memory after ECT and recovery of personal memory, repetition, alertness, orientation, and impersonal memory compared with placebo. Trials varied in cognitive assessment scales, length of therapy, dosing strategy, ECT schedule, and ECT type/parameters. Cholinesterase inhibitors may be effective for reducing cognitive adverse effects of ECT and appear safe and well tolerated. The most commonly studied medication was donepezil 5 mg daily started shortly before and continued throughout ECT. Additional studies are needed to clarify optimal dosing, titration, duration of therapy, and the role of treatment for older adults, preexisting cognitive impairment, and neurologic comorbidities.