Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems.Drug discovery today · 2019Pooled it
- Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study.Journal of psychopharmacology (Oxford, England) · 2020Trial
- Longer-term open-label study of adjunctive riluzole in treatment-resistant depression.Journal of affective disorders · 2019Trial
- Serum and plasma brain-derived neurotrophic factor and response in a randomized controlled trial of riluzole for treatment resistant depression.Journal of affective disorders · 2018Trial
- Current progress in targeted pharmacotherapy to treat symptoms of major depressive disorder: moving from broad-spectrum treatments to precision psychiatry.CNS spectrums · 2025Review
- Sample size calculation for the sequential parallel comparison design with binary endpoint using exact methods.Journal of applied statistics · 2025Article
- Decoding the impact of the placebo response in clinical trials for chronic cough.ERJ open research · 2024Article
- Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target.International journal of molecular sciences · 2024Review
- Randomized trial of ketamine masked by surgical anesthesia in patients with depression.Nature. Mental health · 2023Article
- Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research.Translational psychiatry · 2022Review
- High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens.Molecular psychiatry · 2022Article
- Ketamine and Other Glutamate Receptor Modulating Agents for Treatment-Resistant Depression: A Systematic Review of Randomized Controlled Trials.Iranian journal of psychiatry · 2022Review
- The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders.Nature reviews. Neuroscience · 2022Review
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments.The international journal of neuropsychopharmacology · 2019Review
- The Effect of Glutamatergic Modulators on Extracellular Glutamate: How Does this Information Contribute to the Discovery of Novel Antidepressants?Current therapeutic research, clinical and experimental · 2019Review
- The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?Pharmacology & therapeutics · 2018Review
- Experimental medication treatment approaches for depression.Translational psychiatry · 2017Review
- Prophylactic Efficacy of Riluzole against Anxiety- and Depressive-Like Behaviors in Two Rodent Stress Models.Complex psychiatryArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
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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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.