Course of Improvement in Depressive Symptoms to a Single Intravenous Infusion of Ketamine vs Add-on Riluzole: Results from a 4-Week, Double-Blind, Placebo-Controlled Study

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 37; no. 6; pp. 1526 - 1533
• Main Authors: IBRAHIM, Lobna, DIAZGRANADOS, Nancy, ZARATE, Carlos A, FRANCO-CHAVES, Jose, BRUTSCHE, Nancy, HENTER, Ioline D, KRONSTEIN, Phillip, MOADDEL, Ruin, WAINER, Irving, LUCKENBAUGH, David A, MANJI, Husseini K
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-05-2012
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aged; Antidepressants; Biological and medical sciences; Clinical trials; Controlled conditions; Depression; Depression - drug therapy; Double-Blind Method; Excitatory Amino Acid Antagonists - therapeutic use; Female; Follow-Up Studies; Glutamatergic transmission; Glutamic acid receptors; Humans; Infusions, Intravenous - methods; Intravenous administration; Ketamine; Ketamine - administration & dosage; Ketamine - analogs & derivatives; Ketamine - blood; Male; Medical sciences; Mental depression; Mental health; Middle Aged; Mood disorders; N-Methyl-D-aspartic acid receptors; Neuromodulation; Neuropharmacology; Original; Outcome Assessment (Health Care); Pathophysiology; Pharmacology. Drug treatments; Psychiatric Status Rating Scales; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; R&D; Research & development; Riluzole - therapeutic use; Time Factors; Young Adult; United States > US; Mood disorder; Intravenous administration; Psychotropic; antidepressant; Depression; Glutamate receptor; Anticonvulsant; Neuroprotective agent; Benzothiazole derivatives; Glutamate; Riluzole; Symptomatology; Ketamine; General anesthetic; Perfusion; Placebo; Excitatory aminoacid; Neurotransmitter; Double blind study; NMDA; Antidepressant agent; Drug of abuse; Antagonist; NMDA receptor
• DOI: 10.1038/npp.2011.338
• EISSN: 1740-634X
• ISSN: 0893-133X

The N-methyl-D-aspartate antagonist ketamine has rapid antidepressant effects in patients with treatment-resistant major depression (TRD); these effects have been reported to last for 1 week in some patients. However, the extent and duration of this antidepressant effect over longer periods has not been well characterized under controlled conditions. Riluzole, a glutamatergic modulator with antidepressant and synaptic plasticity-enhancing effects, could conceivably be used to promote the antidepressant effects of ketamine. This study sought to determine the extent and time course of antidepressant improvement to a single-ketamine infusion over 4 weeks, comparing the addition of riluzole vs placebo after the infusion. Forty-two subjects (18-65) with TRD and a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥ 22 received a single intravenous infusion of ketamine (0.5 mg/kg). Four to six hours post-infusion, subjects were randomized to double-blind treatment with either riluzole (100-200 mg/day; n=21) or placebo (n=21) for 4 weeks. Depressive symptoms were rated daily. A significant improvement (P<0.001) in MADRS scores from baseline was found. The effect size of improvement with ketamine was initially large and remained moderate throughout the 28-day trial. Overall, 27% of ketamine responders had not relapsed by 4 weeks following a single ketamine infusion. The average time to relapse was 13.2 days (SE=2.2). However, the difference between the riluzole and placebo treatment groups was not significant, suggesting that the combination of riluzole with ketamine treatment did not significantly alter the course of antidepressant response to ketamine alone.