Riluzole Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder: A Pilot Randomized Placebo-Controlled Trial
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OBJECTIVE: Obsessive-compulsive disorder (OCD) affects approximately 2.5% of the population and is associated with significant morbidity. Many patients receive little benefit from the best available treatments, and even those who do respond often suffer from significant residual symptoms. Convergent evidence suggests that abnormalities in glutamate homeostasis and neurotransmission may contribute to OCD and that glutamate-modulating medications may be of benefit in patients whose symptoms are refractory to standard interventions. Small open-label trials of augmentation of serotonin reuptake inhibitor (SRI) pharmacotherapy with the glutamate modulator riluzole have suggested benefit in adults with refractory symptoms. We report a pilot randomized placebo-controlled trial of riluzole augmentation of ongoing SRI treatment in SRI-refractory patients. METHOD: Outpatients (n = 27) and inpatients (n = 11) with DSM-IV OCD on stable SRI pharmacotherapy were randomized between November 2006 and December 2012 to receive riluzole 50 mg or placebo twice a day and followed for 12 weeks after a 2-week placebo lead-in phase. RESULTS: Riluzole was well tolerated; 1 patient experienced moderate nausea, but none discontinued treatment due to side effects. While there was nominally greater Y-BOCS improvement in the riluzole group (our primary outcome) compared to placebo, it did not reach statistical significance. In the outpatient subsample, a trend suggesting benefit from riluzole augmentation for obsessions (P = .056, 2-tailed, uncorrected) was found in a secondary analysis. Among outpatients, more achieved at least a partial response (> 25% improvement) with riluzole than with placebo (P = .02 in a secondary analysis). CONCLUSIONS: Riluzole may be of benefit to a subset of patients. Larger samples would be required to detect effects of the order suggested by the nominal improvement in our outpatient subsample. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00523718.
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Riluzole reduces clinical symptoms in adults with treatment-refractory OCD when used as add-on to existing pharmacotherapy including SSRIs and antipsychotics.
“Riluzole was shown to reduce clinical symptoms in adults with treatment-refractory OCD when used as add-on to existing pharmacotherapy, including SSRIs and antipsychotics (Coric et al., 2005;Pittenger et al., 2015).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Pittenger et al., 2015
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Treatment Resistance in Obsessive-Compulsive Disorder
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Randomized Controlled Trial of Riluzole Augmentation for Posttraumatic Stress Disorder
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Management of obsessive-compulsive disorder in adults
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Psychotherapy for Treatment-Resistant Obsessive-Compulsive Disorder
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Glutamate Function in Anxiety Disorders and OCD: Evidence from Clinical and Translational Studies
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Obsesif Kompulsif ve İlişkili Bozuklukların Tedavisinde Glutamaterjik Modülatörlerin Rolü
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Behandlung bei psychischer und körperlicher Komorbidität
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Innovation in treating obsessive-compulsive disorder will not solve the care gap
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Neurochemistry and neurotransmitters involved in obsessive–compulsive disorder
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Neuroscience-informed psychoeducation for OCD
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- Authors
- Pittenger, C., Bloch, M. H., Wasylink, S., Billingslea, E., Simpson, R., Jakubovski, E., Kelmendi, B., Sanacora, G., & Coric, V.
- Affiliations
- Yale University (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2015-07-07
- Volume
- 76
- Issue
- 08
- Pages
- 1075-1084
- ISSN
- 0160-6689 (ISSN-L)
- PMC
- PMC4560666
- OpenAlex
- W761557485
- Cited by
- 80
- References
- 57
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 9 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 12 · 2017: 10 · 2016: 4 · 2015: 3
- FWCI
- 11.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH095790, R34MH083115, K08MH081190, R25MH077823)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Keywords
- riluzole, obsessive-compulsive disorder, treatment-refractory OCD, drug augmentation, serotonin reuptake inhibitors, glutamate modulation, glutamate homeostasis, obsession, drug tolerability
- MeSH terms
- Adult, Drug Synergism, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder, Pilot Projects, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Excitatory Amino Acid Antagonists, Riluzole
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