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Cited by 140Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Efficacy and Safety of Basimglurant as Adjunctive Therapy for Major Depression: A Randomized Clinical Trial

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Quiroz, Jorge A., Tamburri, Paul, Deptula, Dennis, Banken, Ludger, Beyer, Ulrich, Rabbia, Michael, Parkar, Nikhat, Fontoura, Paulo +1 more·2016·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2016.0838
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Abstract

IMPORTANCE: Antagonism of the postsynaptic metabotropic glutamate subtype 5 receptor is a novel approach to modulate glutamatergic function and has proven efficacy in a number of preclinical behavioral models of depression. OBJECTIVE: To evaluate the safety and efficacy of basimglurant modified-release (MR) vs placebo as adjunctive therapy to ongoing antidepressant medication therapy in patients with MDD who had inadequate response within the current episode. DESIGN, SETTING, AND PARTICIPANTS: In this phase 2b, double blind, randomized clinical trial of 333 adult patients with a DSM-IV-TR diagnosis of MDD across 59 research clinics globally, patients were assigned to 1 of 2 doses of basimglurant MR (0.5 or 1.5 mg) or placebo once daily, adjunctive to ongoing antidepressant medication therapy (selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor). Patients were enrolled from October 5, 2011, through July 26, 2013. INTERVENTIONS: Six-week treatment with 0.5 mg of basimglurant MR, 1.5-mg basimglurant MR, or placebo once daily, adjunctive to ongoing antidepressant medication therapy. MAIN OUTCOMES AND MEASURES: The primary end point was the mean change from baseline score on the Montgomery-Åsberg Depression Rating Scale (MADRS), as rated by the clinician at week 6. Other measures included patient-rated MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, Clinical Global Impression-Improvement, Patient Global Impression-Improvement, and Clinical Global Impression-Severity Scales and adverse events. RESULTS: A total of 596 patients were screened, and 333 were randomized into the study (mean [SD] age, 47 [11.2] years; 216 female [65.1%]). The primary end point (mean change in clinician-rated MADRS score from baseline to end of treatment) was not met (effect size [ES] = 0.16, P = .42; intent-to-treat [ITT] mixed-effects model for repeated measures [MMRM] analysis for comparing 1.5-mg basimglurant MR and placebo). Across secondary and exploratory end points, 1.5-mg basimglurant MR revealed larger improvements vs placebo on the patient-rated MADRS (-16.2 vs -13.3, ES = 0.28, nominal P = .04), Quick Inventory of Depressive Symptomatology-Self-Report (-7.5 vs -5.8; ES = 0.37, nominal P = .009), Clinical Global Impression-Improvement mean score, and Patient Global Impression-Improvement mean score. Improvements were also seen in the patient-rated MADRS remission rate (36.0% vs 22.0%; nominal P = .03) and response rate (50.5% vs 40.4%; nominal P = .13), A 0.5-mg dose of basimglurant MR had no benefit over placebo in any of these measures. The most common adverse event was dizziness, which was mostly transient and of mild intensity. CONCLUSIONS AND RELEVANCE: No difference was observed on the study's primary outcome measure, the clinician-rated MADRS change from baseline to end of treatment, between adjunctive basimglurant MR vs placebo. Adjunctive 1.5-mg basimglurant MR daily revealed, however, an antidepressant effect across secondary end points, particularly in patient-rated measures. These findings combined with good tolerability warrant further investigation with this compound in depressive disorders. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01437657.

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  1. Quiroz JA, Chen G, Drevets W, Manji HK. Translational approaches to the treatment of mood disorders. In: Barrett JE, Coyle JT, Williams M, eds. Translational Neuroscience: Applications in Neurology, Psychiatry, and Neurodevelopmental Disorders. Cambridge, MA: Cambridge University Press; 2012:27-79.
  2. Guy W, ed. Clinical global impressions (028-CGI). In: ECDEU Assessment Manual for Psychopharmacology. Washington, DC: National Institute of Mental Health, US Dept of Health, Education, and Welfare; 1976:215-222. Publication 76-338.

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Authors
Quiroz, J. A., Tamburri, P., Deptula, D., Banken, L., Beyer, U., Rabbia, M., Parkar, N., Fontoura, P., & Santarelli, L.
Affiliations
  • F. Hoffmann-La Roche AG (CH)
  • Pharmaceutical Research and Early Development, Translational Medicine Neuroscience, Roche Innovation Center, New York, New York
  • Biostatistics, Roche Product Development, Roche Innovation Center, New York, New York
  • Roche (United Kingdom) (GB)
Corresponding author
Quiroz, Jorge A.
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2016-07-01
Volume
73
Issue
7
Pages
675
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2016.0838
OpenAlex
W2428350633
Cited by
133
References
33
Citations by year
2026: 9 · 2025: 8 · 2024: 6 · 2023: 11 · 2022: 10 · 2021: 20 · 2020: 9 · 2019: 15 · 2018: 15 · 2017: 25 · 2016: 4
FWCI
16.73
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
F. Hoffmann-La Roche
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
major depressive disorder, adjunctive therapy, metabotropic glutamate receptor 5, mGlu5 receptor antagonists, glutamatergic modulation, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, drug safety, adverse events, placebo response, antidepressant efficacy
MeSH terms
Adolescent, Adult, Aged, Antidepressive Agents, Delayed-Action Preparations, Depressive Disorder, Major, Major Depressive Disorder, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Imidazoles, Male, Middle Aged, Personality Assessment, Pyridines, Treatment Outcome, Young Adult

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