Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial
Sanjay J. Mathew, James W. Murrough, Marije Aan Het Rot, Katherine A. Collins, David L. Reich, Dennis S. Charney
The International Journal of Neuropsychopharmacology March 17, 2009 DOI: 10.1017/s1461145709000169 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Open-label Peer reviewed |
|---|---|
| Sample size | 26 |
| Population | Patients with treatment-resistant major depression |
| Interventions | Ketamine Lamotrigine Riluzole |
| Dose | 0.5 mg/kg over 40 min (ketamine), 300 mg (lamotrigine), 100-200 mg/d (riluzole) |
| Duration | 32-day continuation trial (riluzole phase) |
| Topics | Depression Ketamine Esketamine |
| Keywords | Riluzole Placebo Lamotrigine Anesthesia Antidepressant Randomized controlled trial Pharmacology Dextromethorphan Glutamate receptor |
| Citations | 295 |
| Key findings | A single sub-anesthetic dose of intravenous ketamine produced rapid antidepressant effects in treatment-resistant depression, but riluzole did not prevent relapse and lamotrigine did not enhance efficacy or reduce side effects. |
Abstract
The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-dose intravenous (i.v.) ketamine; (2) test the efficacy of the glutamate-modulating agent riluzole in preventing post-ketamine relapse; and (3) examine whether pretreatment with lamotrigine would attenuate ketamine's psychotomimetic effects and enhance its antidepressant activity. Twenty-six medication-free patients received open-label i.v. ketamine (0.5 mg/kg over 40 min). Two hours prior to infusion, patients were randomized to lamotrigine (300 mg) or placebo. Seventeen patients (65%) met response criterion (50% reduction from baseline on the Montgomery-Asberg Depression Rating Scale) 24 h following ketamine. Lamotrigine failed to attenuate the mild, transient side-effects associated with ketamine and did not enhance its antidepressant effects. Fourteen patients (54%) met response criterion 72 h following ketamine and proceeded to participate in a 32-d, randomized, double-blind, placebo-controlled, flexible-dose continuation trial of riluzole (100-200 mg/d). The main outcome measure was time-to-relapse. An interim analysis found no significant differences in time-to-relapse between riluzole and placebo groups [log-rank chi(2) = 0.17, d.f. = 1, p = 0.68], with 80% of patients relapsing on riluzole vs. 50% on placebo. The trial was thus stopped for futility. This pilot study showed that a sub-anaesthetic dose of i.v. ketamine is well-tolerated in TRD, and may have rapid and sustained antidepressant properties. Riluzole did not prevent relapse in the first month following ketamine. Further investigation of relapse prevention strategies post-ketamine is necessary.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.