Ketamine and Depression: A Review

Intravenous ketamine is a fast-acting treatment for treatment-resistant depression in both unipolar and bipolar forms. Its benefits last days, longer in unipolar depression, and it may reduce suicidality, though data are limited. Strategies to extend effects—multiple doses, maintenance, or additional medications—have shown mixed results. Alternative routes (intramuscular, intranasal, oral) show promise but lack sufficient data. Adverse effects are mainly mild, transient dissociative and sympathomimetic symptoms, indicating good tolerability. Ketamine's unique properties could shift depression treatment paradigms.

Study at a glance

Abstract

Ketamine, via intravenous infusions, has emerged as a novel therapy for treatment-resistant depression, given rapid onset and demonstrable efficacy in both unipolar and bipolar depression. Duration of benefit, on the order of days, varies between these subtypes, but appears longer in unipolar depression. A unique property is reduction in suicidality although data are more limited. Strategies to extend duration, via multiple doses, maintenance treatment, or subsequent augmenting medications have yielded mixed results. There is a relative paucity of data regarding alternate methods of administration such as intramuscular, intranasal, and oral routes, though preliminary results are promising. Adverse effects most reliably incl ude dissociative and sympathomimetic effects, both transient and mild, and suggest good tolerability. Ketamine's unique effects may represent an opportunity for a paradigm shift in the pharmacologic treatment of depression.