Depression in adults: treatment and management

New published evidence considered in this surveillance review

Intravenous ketamine has been demonstrated to have a rapid antidepressant effect in small randomised trials, however there is uncertainty about its treatment protocols including dosing levels, effectiveness and safety of long-term use in clinical practice.

Intravenous ketamine has been studied across various disorders in mental health, but most commonly in depression and specifically in treatment-resistant depression. The current NICE guideline has recommendations 1.9 around further line treatment in depression, 1.13 electroconvulsive therapy for depression, and 1.15 treatment resistant depression.

The topic proposer positioned intravenous ketamine as an option for the acute treatment of severe or treatment-resistant depression in patients who are considering ECT, which is an effective treatment with a remission rate of 45% and response rate of 65.4% following an acute course of ECT for depressive episode (ECTAS report 2022). The review considered intravenous ketamine in this context.

The topic suggester submitted 4 randomised controlled trials (RCTs) comparing ketamine with ECT, which were included in the systematic reviews considered in this surveillance review.

To date, there have been only 6 RCTs comparing the 2 treatments, and they are therefore used repeatedly in meta-analyses. In Rhee (2025), findings favour ECT over IV ketamine. There are difficulties in comparing studies due to their heterogeneity, including variability in study design, inpatient versus outpatient settings, age of participants, dosage and outcome measures. They also highlight that only 2 trials are well-powered direct comparisons, and these are discussed in more detail below.

The largest trial, Anand (2023), found ketamine to be non-inferior to ECT but used both suboptimal application of the comparator in unilateral ultra-brief pulse ECT and only 6 to 9 sessions. ECTAS monitoring shows the mean number of ECT applications in a course is 10 and the mode is 12. There was also a higher dropout rate after randomisation to the ECT group.

Ekstrand (2021) had the longest follow-up period and administered up to a maximum of 12 ECT sessions. It found that 63% remitted in the ECT group versus 46% receiving intravenous ketamine. More people dropped out of the ketamine group due to side effects, namely the acute dissociative experience. During the 12-month follow up period, those in remission relapsed at similar rates of 63% in the ECT group and 70% in the ketamine group.

The other RCTs, Ghasemi (2014), Kheirabadi (2019), Kheirabadi (2020) and Sharma (2020) include fewer than 40 patients and have limited follow up periods of 3 months or less, which does not reflect the trajectory of the disease.

It is not currently possible to state that intravenous ketamine is equivalent to or superior than ECT and much is unknown about its long-term effects.

This surveillance review did not examine other comparators in depth, for example other augmentation strategies, as reviewed in Terao (2024) or Jelovac (2025).