Effects of Rapastinel (Formerly GLYX-13) on Serum Brain-Derived Neurotrophic Factor in Obsessive-Compulsive Disorder
Omer Linkovski, Ph.D., Hanyang Shen, M.PH., M.S., Jordana Zwerling, M.A., Maria Filippou-Frye, M.D., M.B.S., Booil Jo, Ph.D., Elisabeth Cordell, M.A., Thomas B. Cooper, M.A., Helen Blair Simpson, M.D., Ph.D., Ronald M. Burch, M.D., Ph.D., Joseph R. Moskal, Ph.D., Francis Lee, M.D., Ph.D., Carolyn I. Rodriguez, M.D., Ph.D.
J. Clin. Psychiatry
View details for PubMedID 29505186
Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).
Dell'Osso, B., Benatti, B., Arici, C., Palazzo, C., Altamura, A. C., Hollander, E., Fineberg, N., Stein, D. J., Nicolini, H., Lanzagorta, N., Marazziti, D., Pallanti, S., van Ameringen, M., Lochner, C., Karamustafalioglu, O., Hranov, L., Figee, M., Drummond, L., Rodriguez, C. I., Grant, J., Denys, D., Menchon, J. M., Zohar, J.
View details for PubMedID 28300008
Effect of a Novel NMDA Receptor Modulator, Rapastinel (Formerly GLYX-13), in OCD: Proof of Concept.
Rodriguez, C. I., Zwerling, J., Kalanthroff, E., Shen, H., Filippou, M., Jo, B., Simpson, H. B., Burch, R. M., Moskal, J. R.
THE AMERICAN JOURNAL OF PSYCHIATRY
2016; 173 (12): 1239–41
View details for PubMedID 27903098
Open-Label Trial on the Effects of Memantine in Adults With Obsessive-Compulsive Disorder After a Single Ketamine Infusion
Carolyn I. Rodriguez, Amanda Levinson, Jordana Zwerling, Donna Vermes, and Helen Blair Simpson
JOURNAL OF CLINICAL PSYCHIATRY
View details for PubMedID 27249077
Can expose-based CBT extend the effects of intravenous ketamine in obsessive-complusive disorder? an open-label trial.
Rodriguez, C. I., Wheaton, M., Zwerling, J., Steinman, S. A., Sonnenfeld, D., Galfalvy, H., Simpson, H. B.
JOURNAL OF CLINICAL PSYCHIATRY
2016; 77 (3): 408-409
View details for PubMedID 27046314
Six-Month Outcomes From a Randomized Trial Augmenting Serotonin Reuptake Inhibitors With Exposure and Response Prevention or Risperidone in Adults With Obsessive-Compulsive Disorder
Foa, E. B., Simpson, H. B., Rosenfield, D., Liebowitz, M. R., Cahill, S. P., Huppert, J. D., Bender, J., McLean, C. P., Maher, M. J., Campeas, R., Hahn, C., Imms, P., Pinto, A., Powers, M. B., Rodriguez, C. I., Van Meter, P. E., Vermes, D., Williams, M. T.
JOURNAL OF CLINICAL PSYCHIATRY
2015; 76 (4): 440-446
To compare outcomes after 6-month maintenance treatment of adults diagnosed with obsessive-compulsive disorder (OCD) based on DSM-IV criteria who responded to acute treatment with serotonin reuptake inhibitors (SRIs) augmented by exposure and response prevention (EX/RP) or risperidone.A randomized trial was conducted at 2 academic sites from January 2007 through December 2012. In the acute phase, 100 patients on therapeutic SRI dose with at least moderate OCD severity were randomized to 8 weeks of EX/RP, risperidone, or pill placebo. Responders entered the 6-month maintenance phase, continuing the augmentation strategy they received acutely (n = 30 EX/RP, n = 8 risperidone). Independent evaluations were conducted every month. The main outcome was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).Intent-to-treat analyses indicated that, after 6-month maintenance treatment, EX/RP yielded OCD outcomes that were superior to risperidone (Y-BOCS = 10.95 vs 18.70; t40 = 2.76, P = .009); more patients randomized to EX/RP met response criteria (Y-BOCS decrease ≥ 25%: 70% vs 20%; P < .001) and achieved minimal symptoms (Y-BOCS ≤ 12: 50% vs 5%; P < .001). During maintenance, OCD severity decreased slightly in both conditions (Y-BOCS decrease = 2.2 points, P = .020). Lower Y-BOCS at entry to maintenance was associated with more improvement in both conditions (r38 = 0.57, P < .001).OCD patients taking SRIs who responded to acute EX/RP or risperidone maintained their gains over 6-month maintenance. Because EX/RP patients improved more during acute treatment than risperidone-treated patients, and both maintained their gains during maintenance, EX/RP yielded superior outcomes 6 months later. The findings that 50% of patients randomized to EX/RP had minimal symptoms at 6-month maintenance, a rate double that of prior studies, suggests that EX/RP maintenance helps maximize long-term outcome.ClinicalTrials.gov identifier: NCT00389493.
View details for DOI 10.4088/JCP.14m09044
View details for Web of Science ID 000354997500025
View details for PubMedID 25375780
In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept
Rodriguez, C. I., Kegeles, L. S., Levinson, A., Ogden, R. T., Mao, X., Milak, M. S., Vermes, D., Xie, S., Hunter, L., Flood, P., Moore, H., Shungu, D. C., Simpson, H. B.
2015; 233 (2): 141-7
We previously reported the rapid and robust clinical effects of ketamine versus saline infusions in a proof-of-concept crossover trial in unmedicated adults with obsessive-compulsive disorder (OCD). This study examined the concurrent neurochemical effects of ketamine versus saline infusions using proton magnetic resonance spectroscopy ((1)H MRS) during the clinical proof-of-concept crossover trial. Levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurochemicals glutamate+glutamine (Glx) were acquired in the medial prefrontal cortex (MPFC), a region implicated in OCD pathology. Seventeen unmedicated OCD adults received two intravenous infusions at least 1 week apart, one of saline and one of ketamine, while lying supine in a 3.0T GE MR scanner. The order of each infusion pair was randomized. Levels of GABA and Glx were measured in the MPFC before, during, and after each infusion and normalized to water (W). A mixed effects model found that MPFC GABA/W significantly increased over time in the ketamine compared with the saline infusion. In contrast, there were no significant differences in Glx/W between the ketamine and saline infusions. Together with earlier evidence of low cortical GABA in OCD, our findings suggest that models of OCD pathology should consider the role of GABAergic abnormalities in OCD symptomatology.
View details for DOI 10.1016/j.pscychresns.2015.06.001
View details for PubMedID 26104826
Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder A Randomized Clinical Trial
Simpson, H. B., Foa, E. B., Liebowitz, M. R., Huppert, J. D., Cahill, S., Maher, M. J., McLean, C. P., Bender, J., Marcus, S. M., Williams, M. T., Weaver, J., Vermes, D., Van Meter, P. E., Rodriguez, C. I., PowerS, M., Pinto, A., Imms, P., Hahn, C., Campeas, R.
2013; 70 (11): 1190-1198
Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.clinicaltrials.gov Identifier: NCT00389493.
View details for DOI 10.1001/jamapsychiatry.2013.1932
View details for Web of Science ID 000328948700011
View details for PubMedID 24026523
Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept
Rodriguez, C. I., Kegeles, L. S., Levinson, A., Feng, T., Marcus, S. M., Vermes, D., Flood, P., Simpson, H. B.
2013; 38 (12): 2475-2483
Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (≥35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.
View details for DOI 10.1038/npp.2013.150
View details for Web of Science ID 000325710200016
View details for PubMedID 23783065
Rapid Resolution of Obsessions After an Infusion of Intravenous Ketamine in a Patient With Treatment-Resistant Obsessive-Compulsive Disorder
Rodriguez, C. I., Kegeles, L. S., Flood, P., Simpson, H. B.
JOURNAL OF CLINICAL PSYCHIATRY
2011; 72 (4): 567-569
View details for DOI 10.4088/JCP.10l06653
View details for Web of Science ID 000290012500020
View details for PubMedID 21527129
Minocycline Augmentation of Pharmacotherapy in Obsessive-Compulsive Disorder: An Open-Label Trial
Rodriguez, C. I., Bender, J., Marcus, S. M., Snape, M., Rynn, M., Simpson, H. B.
JOURNAL OF CLINICAL PSYCHIATRY
2010; 71 (9): 1247-1249
iew details for DOI 10.4088/JCP.09l05805blu
View details for Web of Science ID 000282705700022
View details for PubMedID 20923629
Diagnosis and Treatment of a Patient With Both Psychotic and Obsessive-Compulsive Symptoms
Rodriguez, C. I., Corcoran, C., Simpson, H. B.
AMERICAN JOURNAL OF PSYCHIATRY
2010; 167 (7): 754-761
View details for DOI 10.1176/appi.ajp.2009.09070997
View details for Web of Science ID 000279429300008
View details for PubMedID 20595428