Memantine add-on in moderate to severe obsessive-compulsive disorder: Randomized double-blind placebo-controlled study

Ghaleiha, Ali; Entezari, Neda; Modabbernia, Amirhossein; Najand, Babak; Askari, Neda; Tabrizi, Mina; Ashrafi, Mandana; Hajiaghaee, Reza; Akhondzadeh, Shahin

doi:10.1016/j.jpsychires.2012.09.015

Cited by 123 publications

(97 citation statements)

References 40 publications

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“…Memantine has been demonstrated to be an effective augmentation strategy in SRIs in both open label (Aboujaoude et al, 2009;Stewart et al, 2010;Feusner et al, 2009) and a randomized controlled trial (Ghaleiha et al, 2013); however, memantine had a lag time of 8-12 weeks for full clinical benefits in these studies. Two differences might explain the difference in time to clinical effect observed with memantine vs ketamine in the present trial.…”

Section: Discussionmentioning

confidence: 99%

“…Dr Pamela Flood reports an equity interest in Signature Pharmaceuticals. Dr Helen Blair Simpson has received research funds from Janssen Pharmaceuticals (2006)(2007)(2008)(2009)(2010)(2011)(2012) and Transcept Pharmaceuticals (2011-2013, royalties from Cambridge University Press and UpToDate, and consultated for Quintiles (September 2012).…”

Section: Funding and Disclosurementioning

confidence: 99%

“…Moreover, directly disrupting glutamatergic transmission (ie, by deleting a postsynaptic scaffolding protein called SAPAP3; Bienvenu et al, 2008) triggered pathological OCD-like grooming behavior in mice that was reduced by SRI treatment (Welch et al, 2007). Finally, agents that modulate glutamate (eg, riluzole, N-acetylcysteine, and memantine) have been shown to ameliorate OCD symptoms in open (Aboujaoude et al, 2009;Coric et al, 2005;Feusner et al, 2009;Lafleur et al, 2006;Pittenger et al, 2011;Rodriguez et al, 2010;Stewart et al, 2010) and controlled trials (Afshar et al, 2012;Ghaleiha et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Rodríguez

Kegeles

Levinson

et al. 2013

Neuropsychopharmacol

295

204

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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 antiobsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n ¼ 15) with nearconstant 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 (po0.005) 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 ¼ 8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n ¼ 7). One-week post-infusion, 50% of those receiving ketamine (n ¼ 8) met criteria for treatment response (X35% Y-BOCS reduction) vs 0% of those receiving placebo (n ¼ 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.

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Section: Discussionmentioning

confidence: 99%

Section: Funding and Disclosurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Rodríguez

Kegeles

Levinson

et al. 2013

Neuropsychopharmacol

295

204

View full text Add to dashboard Cite

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“…Its use in OCD has been demonstrated in open-label trials [80,81]. A recent RCT found significant improvement in the memantine group compared with controls [82]. It was tried at a dose of 10 mg twice daily and was generally well tolerated.…”

Section: Memantinementioning

confidence: 99%

“…Memantine (20 mg/day) vs placebo + fluoxamine 8 weeks 42 OCD patients Memantine > placebo [82] Bruno et al…”

Section: Reviewmentioning

confidence: 99%

Augmentation strategies in obsessive–compulsive disorder

Arumugham

Reddy

2013

Expert Review of Neurotherapeutics

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Obsessive-Compulsive Disorder

Hirschtritt

Bloch

Mathews

2017

JAMA

338

175

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The dissemination of computer-based cognitive behavioral therapy and improved evidence supporting it represent a major advancement in treatment of OCD. Although cognitive behavioral therapy with or without selective serotonin reuptake inhibitors remains a preferred initial treatment strategy, increasing evidence that supports the safety and efficacy of neuroleptics and neuromodulatory approaches in treatment-resistant cases provides alternatives for patients whose condition does not respond to first-line interventions.

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Memantine add-on in moderate to severe obsessive-compulsive disorder: Randomized double-blind placebo-controlled study

Cited by 123 publications

References 40 publications

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Augmentation strategies in obsessive–compulsive disorder

Obsessive-Compulsive Disorder

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