Pharmacological interventions to diminish cognitive side effects of electroconvulsive therapy: A systematic review and meta‐analysis

Abstract

Objective The authors conducted a systematic review and meta‐analysis of pharmacological interventions to diminish cognitive side effects of ECT. Methods Electronic databases of Pubmed, PsycInfo, Embase and Scopus were searched from inception through 1 April, 2021, using terms for ECT (e.g. electroconvulsive therapy), cognitive outcome (e.g. cogni*) and pharmacological intervention (e.g. calcium channel blocker and general terms, like protein). Original studies with humans receiving ECT were included, which applied pharmacological interventions in comparison with placebo or no additive intervention to diminish cognitive side effects. Data quality was assessed using Risk of Bias and GRADE. Random‐effects models were used. PROSPERO registration number was CRD42021212773. Results Qualitative synthesis (systematic review) showed 52 studies reporting sixteen pharmacological intervention‐types. Quantitative synthesis (meta‐analysis) included 26 studies (1387 patients) describing twelve pharmacological intervention‐types. Low‐quality evidence of efficacy was established for memantine (large effect size) and liothyronine (medium effect size). Very low‐quality evidence shows effect of acetylcholine inhibitors, piracetam and melatonin in some cognitive domains. Evidence of no efficacy was revealed for ketamine (very low‐quality), herbal preparations with anti‐inflammatory properties (very low to low‐quality) and opioid receptor agonists (low‐quality). Conclusion Memantine and liothyronine are promising for further research and future application. Quality of evidence was low because of differences in ECT techniques, study populations and cognitive measurements. These findings provide a guide for rational choices of potential pharmacological intervention research targets to decrease the burden of cognitive side effects of ECT. Future research should be more uniform in design and attempt to clarify pathophysiological mechanisms of cognitive side effects of ECT.

Recent advances in electroconvulsive therapy in clinical practice and research

“…Similarly, donepezil was not found to improve cognitive performance in an RCT that compared donepezil to placebo 38 , 39 . However, a recent meta-analysis found statistically significant improvement in cognitive function with memantine and liothyronine with moderate to large effect sizes, but the quality of the evidence was generally poor due to insufficient number of studies, small sample size, differences in study methodology and risk of bias 40 . The negative outcomes of these studies may be because a different mechanism, not addressed by these drugs, may underlie the cognitive impairment associated with ECT.…”

Medication preventing postictal hypoperfusion and cognitive side-effects in electroconvulsive therapy: A retrospective cohort study

“…Other studies have found functional brain connectivity (fMRI) changes in the salience-, frontoparietal-, and default mode-networks which correlated with cognitive changes ( 9 ). Regarding preventive strategies to diminish cognitive side-effects, a comprehensive meta-analysis has found evidence for protective effects of liothyronine and memantine in ECT, underlining the divergent hypotheses regarding the pathophysiological mechanisms causing postictal confusion and cognitive deterioration after ECT ( 10 ).…”

The effect of transcranial direct current stimulation (tDCS) on cognitive function recovery in patients with depression following electroconvulsive therapy (ECT): protocol for a randomized controlled trial

“…To mitigate or alleviate CSEs, extensive research has been dedicated to pharmacological interventions [15]. Notably, although promising medications like liothyronine [16], memantine [17,18], and galantamine [19] have been reported to potentially alleviate CSEs, further rigorous trials are indispensable to verify their appropriateness for routine clinical application.…”