Review asks how long ketamine's brain-plasticity window lasts and what that means for dosing

The question

How long does ketamine’s effect on brain connections last, and can that timing tell us how often doses should be given for depression?

What they did

Researchers searched two medical databases from their start up to June 2025 for studies that measured both depression symptoms and markers of brain plasticity after ketamine. Brain plasticity here means long-term potentiation and synaptic scaling, two ways brain cells strengthen or rebalance their connections. Two reviewers independently selected studies, extracted data and assessed quality. Sixty-one clinical studies and 17 animal or laboratory studies met the criteria.

What they found

Most clinical studies involved people with treatment-resistant depression, with fewer covering treatment-resistant bipolar depression. A single intravenous ketamine infusion at 0.5 mg/kg produced fast but short-lived antidepressant effects that peaked at 24 hours and faded over 2 to 3 days, with a similar pattern in bipolar depression. Brain activity changes appeared within 3 to 8 hours, settled by 24 hours, and were rarely detected beyond 3 days after treatment. Across trials, dosing twice a week and three times a week gave comparable results at four weeks, and weekly maintenance dosing significantly lowered the risk of relapse. The authors suggest ketamine may open a plasticity window of roughly 2 to 3 days.

The fine print

This is a narrative synthesis, not a pooled statistical analysis, and it combines human studies with animal and laboratory work, which may not translate directly to people. The total number of participants across the included studies is not reported in the abstract, and the quality and design of those studies likely varied. The proposed 2-to-3-day plasticity window is an interpretation of indirect markers, not a tested dosing schedule. This summary is based on the abstract only.

What it means

The review suggests that ketamine’s antidepressant effect and its measurable effects on brain connections both fade within a few days, and that dosing schedules built around that window are worth testing directly.

Evidence grade: Low. A systematic review that mixes 61 clinical studies of varying design with 17 animal studies and reports no pooled statistical analysis.

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