Continuation phase intravenous ketamine in adults with treatment-resistant depression

•Twelve adults (aged 18-64 years) with treatment-resistant unipolar or bipolar I or II major depression were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5 mg/kg, administered over 100 min).•Those who remitted during acute-phase treatment received 4 weekly continuation-phase ketamine infusions, followed by 4 weeks of post-continuation phase follow-up.•Five of the 12 enrollees (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase.•All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment.•Adverse effects were generally mild and transient during acute- and continuation-phase treatment.

BackgroundLittle is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression.MethodsTwelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5 mg/kg, administered over 100 min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24 h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only).ResultsOf the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up.LimitationsThis was an uncontrolled feasibility study with a small sample size.ConclusionsThe continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine.ClinicalTrials.gov identifierNCT02094898.