A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression

Summary & key facts

Researchers tested whether giving intravenous ketamine two or three times a week could keep its fast antidepressant effect in people whose depression had not improved with other treatments. About 67 adults were randomly assigned and neither they nor their doctors knew who got ketamine or a placebo. After about two weeks, ketamine produced much larger drops in a standard depression score than placebo for both schedules. Common side effects included headache, anxiety, brief dissociation, nausea, and dizziness. The study was small and lasted only about two weeks, so it does not tell us about longer-term benefits or harms.

Key facts:

• The study enrolled 67 adults with treatment-resistant depression and randomly assigned them to receive either ketamine or a placebo through an IV two or three times a week.
• After 15 days, people getting ketamine twice a week had their standard depression score fall by about 18 points, compared with about a 6-point drop for placebo.
• People getting ketamine three times a week had a similar drop of about 18 points, compared with about a 3-point drop for placebo after 15 days.
• Both the twice-weekly and thrice-weekly schedules kept the antidepressant effect over the 15-day period and worked similarly to each other.
• Common treatment-related side effects were headache, anxiety, brief feelings of dissociation, nausea, and dizziness; about one in five people experienced these.
• The dissociative symptoms were short-lived and became less strong with repeated doses.
• Patients who switched into an open treatment phase because they didn’t improve initially also tended to show rapid improvement within about four to five days on ketamine.
• The study was small and short, so it cannot say whether ketamine is safe or effective beyond the two-week period tested.

Abstract

OBJECTIVE: Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression. METHOD: In a multicenter, double-blind study, adults (ages 18-64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: In total, 67 (45 women) of 68 randomized patients received treatment. In the twice-weekly dosing groups, the mean change in MADRS score at day 15 was -18.4 (SD=12.0) for ketamine and -5.7 (SD=10.2) for placebo; in the thrice-weekly groups, it was -17.7 (SD=7.3) for ketamine and -3.1 (SD=5.7) for placebo. Similar observations were noted for ketamine during the open-label phase (twice-weekly, -12.2 [SD=12.8] on day 4; thrice-weekly, -14.0 [SD=12.5] on day 5). Both regimens were generally well tolerated. Headache, anxiety, dissociation, nausea, and dizziness were the most common (≥20%) treatment-emergent adverse events. Dissociative symptoms occurred transiently and attenuated with repeated dosing. CONCLUSIONS: Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.

Topics

Anesthesia and Neurotoxicity Research Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Alternative medicine Anesthesia Antidepressant Depression (economics) Dosing Economics Hippocampus Internal medicine Ketamine Macroeconomics Medicine Pathology Placebo Randomized controlled trial Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Anxiety or worry Lack of energy or motivation Sadness or low mood