Advertisement

Preliminary Evidence of Riluzole Efficacy in Antidepressant-Treated Patients with Residual Depressive Symptoms

Published:December 06, 2006DOI:https://doi.org/10.1016/j.biopsych.2006.08.037

      Background

      Excessive glutamatergic neurotransmission may contribute to the pathophysiology of major depressive disorder (MDD). Recent evidence suggests that riluzole and other agents that target glutamate neurotransmission may show antidepressant activity.

      Methods

      Ten patients with treatment-resistant depression had riluzole added to their ongoing medication regimen for 6 weeks, followed by an optional 6-week continuation phase. Depression and anxiety severity were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Linear mixed models were used to test for a linear trend in HDRS and HARS scores across time with treatment.

      Results

      Subjects’ HDRS and HARS scores declined significantly following the initiation of riluzole augmentation therapy. The effect of riluzole was significant at the end of the first week of treatment and persisted for the 12-week duration of the study.

      Conclusions

      These data suggest that riluzole augmentation produces antidepressant and anxiolytic effects in patients with treatment-resistant depression.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Azbill R.D.
        • Mu X.
        • Springer J.E.
        Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes.
        Brain Res. 2000; 871: 175-180
        • Bartanusz V.
        • Aubry J.M.
        • Pagliusi S.
        • Jezova D.
        • Baffi J.
        • Kiss J.Z.
        Stress-induced changes in messenger RNA levels of N-methyl-D-aspartate and AMPA receptor subunits in selected regions of the rat hippocampus and hypothalamus.
        Neuroscience. 1995; 66: 247-252
        • Fava M.
        • Davidson K.G.
        Definition and epidemiology of treatment-resistant depression.
        Psychiatr Clin North Am. 1996; 19: 179-200
        • First M.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.W.
        Structured clinical interview for DSM-IV Axis I disorders—Patient edition (SCID-I/P, version 2.0). Biometric Research Department, New York State Psychiatric Institute, New York1995
        • Frizzo M.E.
        • Dall’Onder L.P.
        • Dalcin K.B.
        • Souza D.O.
        Riluzole enhances glutamate uptake in rat astrocyte cultures.
        Cell Mol Neurobiol. 2004; 24: 123-128
        • Katoh-Semba R.
        • Asano T.
        • Ueda H.
        • Morishita R.
        • Takeuchi I.K.
        • Inaguma Y.
        • et al.
        Riluzole enhances expression of brain-derived neurotrophic factor with consequent proliferation of granule precursor cells in the rat hippocampus.
        FASEB J. 2002; 16: 1328-1330
        • Kugaya A.
        • Sanacora G.
        Beyond monoamines: Glutamatergic function in mood disorders.
        CNS Spectr. 2005; 10: 808-819
        • Mathew S.J.
        • Amiel J.M.
        • Coplan J.D.
        • Fitterling H.A.
        • Sackeim H.A.
        • Gorman J.M.
        Open-label trial of riluzole in generalized anxiety disorder.
        Am J Psychiatry. 2005; 162: 2379-2381
        • Mizuta I.
        • Ohta M.
        • Ohta K.
        • Nishimura M.
        • Mizuta E.
        • Kuno S.
        Riluzole stimulates nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis in cultured mouse astrocytes.
        Neurosci Lett. 2001; 310: 117-120
        • Moghaddam B.
        Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: Comparison to hippocampus and basal ganglia.
        J Neurochem. 1993; 60: 1650-1657
        • Pittenger C.
        • Naungayan C.
        • Kendell S.F.
        • Coric V.
        • Malison R.
        • Krystal J.H.
        • et al.
        Visual hallucinations from the addition of riluzole to memantine and bupropion.
        J Clin Psychopharmacol. 2006; 26: 218-220
        • Risterucci C.
        • Coccurello R.
        • Banasr M.
        • Stutzmann J.M.
        • Amalric M.
        • Nieoullon A.
        The metabotropic glutamate receptor subtype 5 antagonist MPEP and the Na(+) channel blocker riluzole show different neuroprotective profiles in reversing behavioral deficits induced by excitotoxic prefrontal cortex lesions.
        Neuroscience. 2006; 137 ([Epub ahead of publication Oct. 20, 2005]): 211-220
        • Sanacora G.
        • Kendell S.F.
        • Fenton L.
        • Coric V.
        • Krystal J.H.
        Riluzole augmentation for treatment-resistant depression.
        Am J Psychiatry. 2004; 161: 2132
        • Sanacora G.
        • Rothman D.L.
        • Mason G.F.
        • Krystal J.H.
        Clinical studies implementing glutamate neurotransmission in mood disorders.
        in: Moghaddam B. Wolf M.E. Glutamate and Disorders of Cognition and Motivation Ann N Y Acad Sci. 2003: 292-308 (1003)
        • Sapolsky R.M.
        The possibility of neurotoxicity in the hippocampus in major depression: A primer on neuron death.
        Biol Psychiatry. 2000; 48: 755-765
        • Stefani A.
        • Spadoni F.
        • Bernardi G.
        Differential inhibition by riluzole, lamotrigine, and phenytoin of sodium and calcium currents in cortical neurons: Implications for neuroprotective strategies.
        Exp Neurol. 1997; 147: 115-122
        • Trivedi M.H.
        • Rush A.J.
        • Wisniewski S.R.
        • Nierenberg A.A.
        • Warden D.
        • Ritz L.
        • et al.
        Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice.
        Am J Psychiatry. 2006; 163 ([see comment]): 28-40
        • Wang S.J.
        • Wang K.Y.
        • Wang W.C.
        Mechanisms underlying the riluzole inhibition of glutamate release from rat cerebral cortex nerve terminals (synaptosomes).
        Neuroscience. 2004; 125: 191-201
        • Zarate Jr., C.A.
        • Payne J.L.
        • Quiroz J.
        • Sporn J.
        • Denicoff K.K.
        • Luckenbaugh D.
        • et al.
        An open-label trial of riluzole in patients with treatment-resistant major depression.
        Am J Psychiatry. 2004; 161: 171-174
        • Zarate Jr, C.A.
        • Quiroz J.A.
        • Singh J.B.
        • Denicoff K.D.
        • De Jesus G.
        • Luckenbaugh D.A.
        • et al.
        An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression.
        Biol Psychiatry. 2005; 57: 430-432