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

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.

Psychotic depressive subtype and white mater hyperintensities do not predict cognitive side effects in ECT: A systematic review of pretreatment predictors.

BACKGROUND: Most studies regarding cognitive side-effects following ECT for treating depression report transient forms of cognitive disturbances. However, a growing number of studies also report considerable differences among individual patients. OBJECTIVE: The aim of this systematic review was to identify pretreatment patient characteristics for predicting the risk of developing cognitive side-effects following ECT. METHODS: Online databases PubMed/Medline, Embase, and PsycINFO were searched for articles published from 2002 through May 2019, using the following relevant search terms: #cognitive deficits AND #Electro Convulsive Therapy. Inclusion and exclusion criteria were applied for full-text inclusion. PRISMA guidelines were used. RESULTS: Our initial search yielded 2155 publications; 16 studies were included. A total of 16 possible predictive factors were identified. Two factors, psychotic features and white matter hyperintensities, were conclusively found to not predict cognitive side-effects following ECT; the remaining 14 factors were inconclusive. CONCLUSIONS: There is robust evidence that psychotic features and white matter hyperintensities are not predictive of cognitive side-effects following ECT. None of the other 14 factors examined were predictive, however these levels of evidence were weak and therefore inconclusive. Additional studies focusing primarily on pretreatment patient characteristics for predicting cognitive side-effects following ECT are needed, including demographic, clinical, physiological, neurobiological, and genetic factors. Finally, we provide suggestions for future research.