A review of ketamine’s role in ECT and non-ECT settings

Abstract

Up to 20% of depressed patients demonstrate treatment resistance to one or more adequate antidepressant trials, resulting in a disproportionately high burden of illness. Ketamine is a non-barbiturate, rapid-acting general anesthetic that has been increasingly studied in treatment resistant depression (TRD), typically at sub-anesthetic doses (0.5 mg/kg over 40 min by intravenous infusion). More recent data suggest that ketamine may improve response rates to electroconvulsive therapy (ECT) when used as an adjunct, but also as a sole agent. In the ECT setting, a dose of 0.8 mg/kg or greater of ketamine demonstrates improved reduction in depressive symptoms than lower doses; however, inconsistency and significant heterogeneity among studies exists. Clinical predictors of responses to ketamine have been suggested in terms of non-ECT settings. Ketamine does increase seizure duration in ECT, which is attenuated when concomitant barbiturate anesthetics are used. However, most studies are small, with considerable heterogeneity of the sample population and variance in dosing strategies of ketamine, ECT, and concomitant medications, and lack a placebo control, which limits interpretation. Psychotomimetic and cardiovascular adverse effects are reported with ketamine. Cardiovascular adverse effects are particularly relevant when ketamine is used in an ECT setting. Adverse effects may be mitigated with concurrent propofol; however, this adds complexity and cost compared to standard anesthesia. Long-term adverse effects are still unknown, but relevant, given recent class concerns for anesthetic and sedative agents.

Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials

“…We also added one further (post hoc) subgroup analysis. Specifically, given recent findings that ketamine may accelerate the effect of ECT in patients with treatmentresistant depression (Jankauskas et al, 2018), we excluded those studies in which ketamine was administered as part of ECT treatment. a1,a6,a10 Excluding these trials did not materially affect either the direction or magnitude of effect for ketamine for any time point.…”

Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review

“…6,45 Likewise, ketamine's effect has been identified in patients who are currently taking other antidepressant medications, as well as those who are drug-free or have completed a washout period. 6,41,46,49…”

“…All systematic review or meta-analytic articles noted rapid onset of ketamine's antidepressant effect among patients with MDD. 3,4,[6][7][8][9]14,15,[40][41][42][43][44][45][46][47][48][49][50][51][52][53] Meta-analyses, which primarily focused on a single intravenous infusions, identified lower mean depression severity and remission in ketamine groups relative to placebo, with onset between 1 and 24 h post-infusion, 6,9,14,40,41,43,45,47,50,52 and typically persisting for 1-2 weeks. 3,8,9,14,[41][42][43]45,47,49,50 Repeated administrations of ketamine of up to six doses produce a more pronounced antidepressant effect at the 2-week follow-up relative to a single administration, 43,44,50 and prolonged time to relapse.…”

Ketamine Anesthesia in Electroconvulsive Therapy

“…On the other hand, even if ketamine prolongs the duration of seizures, according to some reports, ketamine is not better than other anesthetics in reducing depressive symptoms or improving cognition [16,[20][21][22][23]. The effect of ketamine on the duration of seizures during ECT has been evaluated differently in each study, and the ECT protocols vary from institution to institution making efficacy assessment difficult [11]. The additional problem is that the assessment items (seizure duration, early stage of rapport, or cognitive improvement) do not match.…”