Ketamine accelerates the antidepressive effect of electroconvulsive therapy in patients with depressive disorder, especially when ketamine is used as an add-on anesthetic, according to a study published in the Journal of Psychiatric Research. The accelerated effect of ketamine is not reflected in the final electroconvulsive therapy course outcome, however, and requires careful administration due to an increased risk for adverse events.

Researchers sought to assess whether ketamine could enhance the antidepressive effect of electroconvulsive therapy used in patients with depressive disorder. Furthermore, they aimed to compare the difference in therapeutic effects when ketamine was used in monotherapy vs as an add-on agent in electroconvulsive therapy.

Researcherssearched relevant databases, including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO, for randomized controlled trials that assessed the efficacy of ketamine used in electroconvulsive therapy. They extracted data from 16 studies including a total of 928 patients diagnosed with depressive disorder. Participants’ depressive symptoms were assessed postelectroconvulsive therapy using either the Hamilton Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale, or the Beck Depression Inventory. Secondary outcomes measured participant response rate and remission rate; tolerability was measured by adverse events and cognitive function outcomes.

Of the 16 eligible studies, ketamine was used as an anesthetic alone in 6 studies, as an add-on anesthetic in 7 studies, or as both in 3 studies. A significant difference in depressive scores was observed in favor of ketamine after the 1st, 3rd, 4th, 5th, and 6th electroconvulsive therapy sessions; whereas no significant difference was observed after the 2nd, 8th, 10th, and 12th sessions.

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When ketamine was used as an add-on anesthetic, depressive scores were lower after the 2nd, 3rd, 4th, and 6th sessions, but not after the 1st, 5th, 8th, 10th, and 12th sessions. Ketamine used alone showed the opposite trend: depressive scores were lowest after the 1st electroconvulsive therapy session. The investigators observed no significant therapeutic advantage that prioritized ketamine at the end of the electroconvulsive therapy course in any group.

Response and remission rates of ketamine in electroconvulsive therapy showed no significant difference from the comparator groups; however, the researchers observed no increased adverse events in ketamine usage for electroconvulsive therapy. Ketamine was associated with higher rates of psychiatric adverse events (agitation, confusion, hallucination, delirium) and cardiovascular events (hypertension, tachycardia, increased blood pressure or heart rate). Additional adverse events associated with ketamine were reported, including nausea, vomiting, fatigue, headache, disorientation, sense of fear, musculoskeletal and connective tissue disorders, and infection.

Limitations of the study included the 6 studies rated as low quality due to the risk of performance bias, blinding of participants, or assessment of highly subjective outcomes (depression or pain). The study could not declare the optimal electroconvulsive therapy pattern for patients and did not include follow-up data, limiting the ability to determine long-term efficacy and tolerability differences.

Although a rapid antidepressive effect was observed early on in patients receiving ketamine, especially as an add-on anesthetic, by the end of the electroconvulsive therapy course, ketamine did not significantly reduce depressive symptoms. Furthermore, an increased risk for adverse effects requires cautious administration of ketamine in electroconvulsive therapy. Due to its accelerating effect, the investigators suggest that ketamine would be more efficacious used in short to moderate electroconvulsive therapy courses.

This study was supported by the National Natural Science Foundation of China, the National Key Clinical Specialty Construction Project, and the Chongqing Medical Key Discipline Construction Project.

Reference

Ren L, Deng J, Min S, Peng L, Chen Q. Ketamine in electroconvulsive therapy for depressive disorder: a systematic review and meta-analysis [published online July 7, 2018]. J Psychiatr Res. 2018; 104:144-156.