title: Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized, double-blind, placebo-controlled trial.
abstract: Recent evidences suggest that glutamatergic dysregulation implicated in neural plasticity and cellular resilience may contribute to the pathophysiology of Major Depressive Disorder (MDD). Riluzole, which exerts its effect by targeting glutamate neurotransmission, has shown antidepressant effect in recent preclinical, observational and open label studies. This study aimed to assess the efficacy and tolerability of riluzole in patients with MDD. Sixty-four inpatients with diagnosis of moderate to severe major depressive disorder participated in a parallel, randomized, controlled trial, and sixty patients underwent 6 weeks treatment with either riluzole (50 mg/bid) plus citalopram (40 mg/day) or placebo plus citalopram (40 mg/day). All participants were inpatients for the whole duration of the study. Patients were assessed using Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4 and 6. The primary outcome measure was to assess the efficacy of riluzole compared to placebo in improving the depressive symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on HDRS [F (1.86, 107.82) = 8.63, p < 0.001]. Significantly greater improvement was observed in HDRS scores in the riluzole group compared to the placebo group from baseline HDRS score at weeks 2, 4 and 6 (p < 0.001, p = 0.001, p = 0.002, respectively). Significantly greater response with greater speed to treatment was observed in the riluzole group than the placebo group. No serious adverse event occurred. This study showed a favorable safety and efficacy profile in patients with major depressive disorder. Larger controlled studies with longer treatment periods are needed to investigate long term safety, efficacy and optimal dosing.
authors.affiliation: Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Salardini
authors.affiliation: Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Zeinoddini
authors.affiliation: Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Mohammadinejad
authors.affiliation: Razi Hospital, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Khodaie-Ardakani
authors.affiliation: Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nagmeh
authors.initials: N
authors.lastname: Zahraei
authors.affiliation: Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arefeh
authors.initials: A
authors.lastname: Zeinoddini
authors.affiliation: Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: s.akhond@neda.net.
authors.forename: Shahin
authors.initials: S
authors.lastname: Akhondzadeh
mesh_terms: D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D019782:Riluzole / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D018696:Neuroprotective Agents; D015283:Citalopram; D019782:Riluzole
keywords: Clinical trial; Glutamate; Major depression disorder; Riluzole