Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Nov 1:258:102-108.
doi: 10.1016/j.jad.2019.06.065. Epub 2019 Jul 2.

Longer-term open-label study of adjunctive riluzole in treatment-resistant depression

Hitoshi Sakurai  1 , Christina Dording  2 , Albert Yeung  2 , Simmie Foster  2 , Felipe Jain  2 , Trina Chang  2 , Nhi-Ha Trinh  2 , Richard Bernard  2 , Sean Boyden  2 , Syed Z Iqbal  3 , Samuel T Wilkinson  4 , Sanjay J Mathew  3 , David Mischoulon  2 , Maurizio Fava  2 , Cristina Cusin  5
Affiliations
Clinical Trial

Longer-term open-label study of adjunctive riluzole in treatment-resistant depression

Hitoshi Sakurai et al. J Affect Disord. .

Abstract

Background: While riluzole has been investigated for the treatment of depression, little is known about its longer-term efficacy and optimal treatment duration in treatment-resistant depression (TRD). The objective of this study is to characterize the longer-term outcome of adjunctive riluzole therapy for TRD in an open-label extension of an 8-week acute treatment trial.

Methods: The data from 66 patients with TRD who received adjunctive riluzole in a 12-week open-label extension phase were analyzed. Response rates (⩾50% reduction in the Mongomery-Asberg Depression Rating Scale [MADRS] score), relapse rates (a MADRS score of ⩾22 in patients who had previously achieved response), and adverse events were examined in patients who had achieved response at the end of the acute phase and those who had not.

Results: Among acute phase responders, the maintained response rate was 66.7% (8/12) and the relapse rate was 8.3% (1/12). In acute phase non-responders, the response rate was 24.1% (13/54). The most commonly reported adverse event was fatigue (9.1%). Three cases were considered serious adverse events; vomiting (n = 1), shortness of breath (n = 1), and aborted suicide attempt (n = 1).

Limitations: This longer-term study was open-label and uncontrolled. The sample size was relatively small.

Conclusions: Longer-term adjunctive riluzole appears relatively well tolerated and beneficial for maintaining previous response. Additionally, approximately one fourth of patients who did not respond to 8-week antidepressant treatment might respond if treated with riluzole for 12 weeks. Those findings warrant further investigation because adjunctive riluzole could represent an option for treatment of depression when standard antidepressants have failed.

Keywords: Longer-term; Relapse; Response; Riluzole; Tolerability; Treatment-resistant depression.

PubMed Disclaimer

Conflict of interest statement

Declarations of interest:

Dr. Sakurai has received manuscript or speaker’s honoraria from Dainippon Sumitomo, Eli Lilly, Meiji-Seika Pharma, Otsuka Pharmaceutical, Tanabe Mitsubishi Pharma, and Yoshitomi Yakuhin within the past three years. He also receives support from the Japanese Society of Clinical Neuropsychopharmacology. Dr. Chang had stock of Abbott and Shire Pharmaceuticals and received support from an NIDDK career development award. Dr. Wilkinson reports research funding and consulting fees from Janssen. He also receives support from the Agency for Healthcare Research and Quality (K12HS023000) and from the Brain and Behavioral Research Foundation (formerly NARSAD), the Robert E. Leet and Clara Guthrie Patterson Trust, and the American Foundation for Suicide Prevention. Dr. Mathew is supported by the use of facilities and resources at the Michael E. Debakey VA Medical Center, Houston, Tx. He has served as a consultant to Alkermes, Bracket, Clexio, Janssen, Perception, and Sage Therapeutics. He has received research support from Biohaven, NeuroRx, and Vistagen. Dr. Mischoulon has received research support from Nordic Naturals. He has provided unpaid consulting for Pharmavite LLC and Gnosis USA, Inc. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Blackmores, and PeerPoint Medical Education Institute, LLC. He has received royalties from Lippincott Williams & Wilkins for published book “Natural Medications for Psychiatric Disorders: Considering the Alternatives.” Dr. Fava reports 3-year disclosures as below: all lifetime disclosures can be view on line at: http://mghcme.org/faculty/faculty-detail/maurizio_fava; research support: Abbott Laboratories; Acadia Pharmaceuticals; Alkermes, Inc.; American Cyanamid;Aspect Medical Systems; AstraZeneca; Avanir Pharmaceuticals; AXSOME Therapeutics; Biohaven; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Cerecor; Clarus Funds; Clintara, LLC; Covance; Covidien; Eli Lilly and Company;EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; FORUM Pharmaceuticals; Ganeden Biotech, Inc.; GlaxoSmithKline; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenix; Janssen R&D, LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck Inc.; Marinus Pharmaceuticals; MedAvante; Methylation Sciences Inc; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM);National Coordinating Center for Integrated Medicine (NiiCM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Neuralstem, Inc.; NeuroRx; Novartis AG; Organon Pharmaceuticals; Otsuka Pharmaceutical Development, Inc.; PamLab, LLC.; Pfizer Inc.; Pharmacia-Upjohn; Pharmaceutical Research Associates., Inc.; Pharmavite® LLC; PharmoRx Therapeutics; Photothera; Reckitt Benckiser; Roche Pharmaceuticals; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Stanley Medical Research Institute (SMRI); Synthelabo; Taisho Pharmaceuticals; Takeda Pharmaceuticals; Tal Medical; VistaGen; Wyeth-Ayerst Laboratories; advisory board/ consultant: Abbott Laboratories; Acadia; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Avanir Pharmaceuticals; AXSOME Therapeutics; Bayer AG; Best Practice Project Management, Inc.; Biogen; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; Boehringer Ingelheim; Boston Pharmaceuticals; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Cerecor; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Forum Pharmaceuticals; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; Indivior; i3 Innovus/Ingenis; Intracellular; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; Marinus Pharmaceuticals; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Navitor Pharmaceuticals, Inc.; Nestle Health Sciences; Neuralstem, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Osmotica; Otsuka Pharmaceuticals; Pamlab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite® LLC.; PharmoRx Therapeutics; Praxis Precision Medicines; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; PPD; Purdue Pharma; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Relmada Therapeutics, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Shenox Pharmaceuticals; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Taisho Pharmaceuticals; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex; Teva Pharmaceuticals; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Usona Institute,Inc.; Vanda Pharmaceuticals, Inc.; Versant Venture Management, LLC; VistaGen; speaking/publishing: Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/Physicians Postgraduate Press, Inc.; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource,Corp.; Wyeth-Ayerst Laboratories.; equity holdings: Compellis; PsyBrain, Inc.; royalty/patent, other income: Patents for Sequential Parallel Comparison Design (SPCD), licensed by MGH to Pharmaceutical Product Development, LLC (PPD) (US_7840419, US_7647235, US_7983936, US_8145504, US_8145505); and patent application for a combination of Ketamine plus Scopolamine in Major Depressive Disorder (MDD), licensed by MGH to Biohaven. Patents for pharmacogenomics of Depression Treatment with Folate (US_9546401, US_9540691). Copyright for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), Symptoms of Depression Questionnaire (SDQ), and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing Co. Pte.Ltd. Dr Cusin has received speaking and consulting fees from Janssen, Takeda, Boehringer, Alkermes. –Equity: None. –Royalty/patent: PCT/US15/56192; 070919.00032 Acyclic cucurbit[N]uril type molecular containers to treat intoxication and substance abuse. Dr. Dording has nothing to declare. Dr. Yeung has nothing to declare. Dr. Foster has nothing to declare. Dr. Jain has nothing to declare. Dr. Trinh has nothing to declare. Mr. Bernard has nothing to declare. Mr. Boyden has nothing to declare. Dr. Iqbal has nothing to declare.

Figures

Figure 1.
Figure 1.
Patient Flow
Figure 2.
Figure 2.. Time to Non-response in Acute Phase Responders
No statistically significant differences were found between the RIL-R group and PBO-R group (Log-rank statistic=0.24, p=0.62). PBO-R, Placebo responder; RIL-R, Riluzole responder
See this image and copyright information in PMC

References

    1. Abdallah CG, Jiang L, De Feyter HM, Fasula M, Krystal JH, Rothman DL, Mason GF, Sanacora G, 2014. Glutamate metabolism in major depressive disorder. Am J Psychiatry. 171, 1320–1327. 10.1176/appi.ajp.2014.14010067 - DOI - PMC - PubMed
    1. Albo F, Pieri M, Zona C, 2004. Modulation of AMPA receptors in spinal motor neurons by the neuroprotective agent riluzole. J Neurosci Res. 78, 200–207. 10.1002/jnr.20244 - DOI - PubMed
    1. Baldessarini RJ, Forte A, Selle V, Sim K, Tondo L, Undurraga J, Vázquez GH, 2017. Morbidity in Depressive Disorders. Psychother Psychosom. 86, 65–72. 10.1159/000448661 - DOI - PubMed
    1. Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G, 2010. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry. 15, 501–511. 10.1038/mp.2008.106 - DOI - PMC - PubMed
    1. Brennan BP, Hudson JI, Jensen JE, McCarthy J, Roberts JL, Prescot AP, Cohen BM, Pope HG Jr., Renshaw PF, Ongür D, 2010. Rapid enhancement of glutamatergic neurotransmission in bipolar depression following treatment with riluzole. Neuropsychopharmacology. 35, 834–846. 10.1038/npp.2009.191 - DOI - PMC - PubMed

Publication types