Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized, double-blind, placebo-controlled trial

Salardini, Elaheh; Zeinoddini, Atefeh; Mohammadinejad, Payam; Khodaie‐Ardakani, Mohammad‐Reza; Zahraei, Nagmeh; Zeinoddini, Arefeh; Akhondzadeh, Shahin

doi:10.1016/j.jpsychires.2016.01.003

Cited by 46 publications

(38 citation statements)

References 44 publications

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“…However, these studies were not designed to directly examine the antidepressant effects of riluzole and were not powered to detect moderate sized effects. In contrast, a recent placebo-controlled trial of riluzole conducted in 60 non-resistant MDD Iranian patients showed efficacy; in this 6-week inpatient study, the combination of riluzole and citalopram was found to be superior to the combination of citalopram and placebo with large effect sizes (Cohen's d40.8 at weeks 2, 4, and 6 of treatment, which was every time point examined) (Salardini et al, 2016).…”

Section: Introductioncontrasting

confidence: 62%

A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder

Mathew

Gueorguieva

Brandt

et al. 2017

Neuropsychopharmacol.

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Riluzole is a glutamate-modulating agent with neuroprotective properties approved for use in amyotrophic lateral sclerosis. The efficacy and safety of riluzole vs placebo as an adjunct to antidepressant medication in outpatients with major depressive disorder (MDD) was examined in a 3-site, 8-week, randomized, double-blind, placebo-controlled, fixed-dose trial using a sequential parallel comparison design comprised of two phases of 4 weeks. Patients with MDD in a current major depressive episode (N=104) with an inadequate response to either a prospective or a historical trial of an antidepressant medication were randomized in a 2 : 3 : 3 ratio to the treatment sequences of riluzole/riluzole, placebo/placebo, and placebo/riluzole, respectively. The primary outcome was change in depression severity, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary efficacy outcomes included the response rate, defined as at least a 50% improvement in MADRS, Clinical Global Impressions severity and improvement subscales, and patient-reported measures of depression and cognitive function. Eighty-five patients completed the randomized treatment phases. Treatment groups did not differ in mean change in MADRS scores, response rate, or in any secondary efficacy outcomes. Riluzole was generally well tolerated, with a side effect profile consistent with its clinical use. In conclusion, a fixed dose of riluzole (100 mg/day) did not show adjunctive antidepressant efficacy compared to placebo. The trial was adequately powered to detect a moderate riluzole effect, and the risk for exaggerated placebo responses was mitigated. The lack of efficacy suggests that mechanisms underlying riluzole's neuroprotective effects are insufficient for clinical response in treatment-resistant depression.

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Section: Introductioncontrasting

confidence: 62%

A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder

Mathew

Gueorguieva

Brandt

et al. 2017

Neuropsychopharmacol.

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“…The glutamatergic dysfunction implicated in neural plasticity and cellular resilience may then contribute to the pathophysiology of depressive disorder, and riluzole was evaluated as a treatment for depression in both human and rodents [28]. A recent preclinical, observational, open-label study showed great improvement in the riluzole group compared to the placebo group [29,30]. In the present study, riluzole showed dramatic amelioration of sucrose consumption, latency, and food intake in the behavioral paradigm compared to the CUMS model group.…”

Section: Discussionmentioning

confidence: 99%

Mechanism Underlying Acupuncture-Ameliorated Depressive Behaviors by Enhancing Glial Glutamate Transporter in Chronic Unpredictable Mild Stress (CUMS) Rats

Luo

et al. 2017

Med Sci Monit

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BackgroundMajor depressive disorder (MDD) is a recurrent mental illness worldwide. The glutamatergic neurotransmission system is now a target for antidepressant therapy because it takes part in synaptic plasticity and cognition in physical condition and has a potential excitatory neurotoxicity in pathological conditions. Glial glutamate transporter EAAT2 performs 90% of Glu neurotransmission. Therefore, the aim of the study was to evaluate the effect of acupuncture on depressive behaviors and EAAT2 in CUMS.Material/MethodsWe randomly divided 56 male SD rats into a normal group, a model group, an acupuncture group, and a riluzole group. Rats in the model group, acupuncture group, and riluzole group underwent chronic unpredictable mild stress (CUMS) exposure for 21 days. The acupuncture group received electro-acupuncture stimulation on LI4 and LR3 for 5 continuous days per week for 4 weeks, and rats in the riluzole group received 4 mg/kg of riluzole orally (Sanofi, J20140092) for 4 weeks after undergoing CUMS stimulation.ResultsRats showed significantly increased sucrose consumption in the sucrose preference test paradigm, and showed elevated food intake and shortened latency in the novelty-suppressed feeding test paradigm after undergoing acupuncture therapy and riluzole treatment. The amelioration of depressive behavioral actions was consistent with increasing number of positive cells, protein, and mRNA expression of glial glutamate transporter EAAT2 in the hippocampus and PFC.ConclusionsThe results suggest that acupuncture and riluzole are both effective in improving sucrose consumption, latency, and food intake in CUMS rats. However, acupuncture appears to achieve an antidepressant effect later than riluzole does because it might need accumulated stimulation by enhancing EAAT2 expression. Enhance glial glutamate transporter EAAT2 in the hippocampus and PFC is a mechanism underlying the antidepressant effect of acupuncture.

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“…The Extrapyramidal Symptom Rating Scale (ESRS; part one: Parkinsonism, dystonia, and dyskinesia; the sum of 11 items; Chouinard & Margolese, ) was used to assess the extrapyramidal symptoms at baseline and at weeks 2, 4, 6, and 8. Depressive symptoms (mainly to exclude significant depression) were assessed with the HDRS (validated 17‐item rating scale, which has been used in many trials in Iran (Abbasi et al, ; Arabzadeh et al, ; Gougol et al, ; Salardini et al, ) at baseline and at weeks 2, 4, 6, and 8.Two trained raters (third‐year residents of psychiatry) were responsible for rating the patients with an interreliability of >90% on PANSS total symptoms. The primary outcome measure of this study was the evaluation of cilostazol efficacy in improvement of schizophrenia negative symptoms (reduction in PANSS negative subscale score from baseline to the study end) compared to placebo.…”

Section: Methodsmentioning

confidence: 99%

Cilostazol adjunctive therapy in treatment of negative symptoms in chronic schizophrenia: Randomized, double-blind, placebo-controlled study

Rezaei

Mesgarpour²,

Jeddian

et al. 2017

Hum. Psychopharmacol Clin Exp

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Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized, double-blind, placebo-controlled trial

Cited by 46 publications

References 44 publications

A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder

A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder

Mechanism Underlying Acupuncture-Ameliorated Depressive Behaviors by Enhancing Glial Glutamate Transporter in Chronic Unpredictable Mild Stress (CUMS) Rats

Cilostazol adjunctive therapy in treatment of negative symptoms in chronic schizophrenia: Randomized, double-blind, placebo-controlled study

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