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Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial

  • Sanjay J. Mathew (a1), James W. Murrough (a1), Marije aan het Rot (a1), Katherine A. Collins (a1), David L. Reich (a2) and Dennis S. Charney (a1) (a3) (a4) (a5)...

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 χ2=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.

Corresponding author
Address for correspondence: S. J. Mathew, M.D., Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy PlaceBox 1217, New York, NY10029, USA. Tel.: (212) 241-4480Fax: (212) 241-3354Email:
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