Review of repeated ketamine "maintenance" doses for hard-to-treat depression

The question

Once ketamine has helped someone with depression that has not responded to other treatments, does continuing with ongoing “maintenance” doses keep the benefit going, and is it safe?

What they did

Researchers searched major medical databases for studies published between January 2020 and November 2024 that looked at ketamine maintenance therapy in treatment-resistant depression. Eleven studies met their criteria. They rated the quality of randomized trials with the Cochrane Risk of Bias 2 tool and the quality of observational studies with the Newcastle-Ottawa Scale. The review followed PRISMA reporting guidelines.

What they found

Giving maintenance doses on a regular schedule was linked to fewer relapses than giving them on a flexible or variable schedule (27.3 per cent versus 45.6 per cent). Better response was reported in people under 45 and in those whose depression had lasted less than two years. Adding psychotherapy alongside ketamine was associated with staying well longer (hazard ratio 0.72 for relapse). Side effects were described as generally mild to moderate, and 7.2 per cent of people stopped treatment.

The fine print

Only 11 studies were included, and they combined randomized trials with observational research, so the comparisons between dosing schedules are not the same as a head-to-head randomized test. The abstract does not report how many people were involved in total, how long they were followed, or the doses used. Findings about age and depression duration come from comparisons across studies and may reflect who was selected for treatment rather than a true effect. This summary is based on the abstract alone.

What it means

Continuing ketamine on a regular schedule may help some people with treatment-resistant depression stay well, but the underlying evidence is limited and mixed, and the best schedule and duration are still unknown.

Evidence grade: Low. A systematic review of only 11 studies that mixes randomized trials with observational research, reports no pooled participant total, and compares protocols narratively rather than through a formal pooled analysis.

This summary is based on the study’s published abstract.