Ketamine can quickly reduce depression in people who do not respond to other treatments, but the effect often fades. Maintenance ketamine treatment—repeated doses over time—may help sustain the antidepressant benefit. A review of three randomized trials, eight open-label studies, and 30 case series found that intravenous, intranasal, oral, and possibly intramuscular and subcutaneous maintenance ketamine are effective for sustaining antidepressant effects in treatment-resistant depression. Serious side effects such as tolerance, cognitive problems, addiction, and kidney or urinary issues appear uncommon. Despite limitations in the available studies, maintenance ketamine shows therapeutic potential. More controlled and naturalistic long-term research is needed to clarify its role in routine care.
Ketamine is known to have rapid antidepressant effects, but patients with psychotic features are usually excluded from treatment studies due to concerns that ketamine might worsen psychosis. This systematic review examined nine reports (pilot studies and case reports) involving 41 patients with a history of psychosis or current psychotic symptoms who received ketamine for depression or negative symptoms. The findings suggest that short-term ketamine treatment can be both safe and effective in this group, with side effects that were mild and self-limiting. The available evidence does not support the assumption that ketamine exacerbates psychotic symptoms in predisposed patients, although data are limited and further trials are needed.