Intravenous ketamine at 0.5 mg/kg and 1.0 mg/kg produces rapid antidepressant effects in adults with treatment-resistant depression, with most improvement seen one day after a single 40-minute infusion. Lower doses (0.1 mg/kg and 0.2 mg/kg) did not show consistent benefit. The study compared four ketamine doses against an active placebo (midazolam) in 99 outpatients across six U.S. sites. Higher doses caused more dissociative symptoms and temporary blood pressure increases, but infusions were generally well tolerated. The findings indicate a range of effective subanesthetic doses, with no clear advantage for doses below 0.5 mg/kg.
In a retrospective analysis of 537 patients receiving ketamine intravenous therapy for depression in 178 U.S. community practices, 53.6% showed a response (at least 50% reduction in depression scores) and 28.9% achieved remission within 14-31 days after the induction phase. Among patients with suicidal ideation at baseline, 73.0% reported a reduction. A small portion of patients worsened: 8.4% experienced increased depressive symptoms and 6.0% reported increased suicidal ideation. Response rates were similar across levels of baseline depression severity. Patients who responded had about an 80% chance of sustaining that response at 4 weeks and about 60% at 8 weeks, even without maintenance infusions.
A single intravenous infusion of ketamine may reduce suicidal ideation in patients with treatment-resistant depression for up to 30 days, but early effects diminish rapidly. In a double-blind randomized trial, 40 patients received ketamine and 16 received midazolam placebo; all had clinically significant suicidal ideation at baseline. By day 30, the ketamine group had a lower mean suicide score (2.03) than the placebo group (3.00). However, among those whose suicidal ideation initially resolved by day 3, there was no significant difference between groups in later scores. Recurrence of suicidal ideation was common in both groups. The findings suggest a possible role for ketamine as an adjunct to standard treatments.