Memantine Treatment for Obsessive-compulsive Disorder and Generalized Anxiety Disorder

Phase

Condition

Panic Disorders

Obsessive-compulsive Disorder

Mood Disorders

Treatment

N/A

Clinical Study ID

NCT00674219

04-08-063-03

Ages 18-64
All Genders

Study Summary

The objective of this study was to obtain preliminary open-label data on the efficacy and tolerability of memantine, an anti-glutamatergic medication with a unique pharmacodynamic profile, in individuals with OCD and individuals with GAD. Because glutamatergic hyperactivity in frontal and frontal-subcortical circuits may play a role in the symptomatic expression of OCD, and possibly GAD, agents that reduce glutamatergic neurotransmission should provide unique anti-stress and anti-obsessional benefits. Memantine is a specific, uncompetitive antagonist at the NMDA receptor that blocks sustained activation of the NMDA receptor by high concentrations of glutamate under pathological conditions but rapidly leaves the NMDA channel upon transient physiological activation by low concentrations of glutamate.

Eligibility Criteria

Inclusion

Inclusion Criteria:

The subject is male or female outpatient between 18-64 years old.
The subject meets DSM-IV criteria for Generalized Anxiety Disorder or ObsessiveCompulsive Disorder as determined by the MINI.
Sexually active female patients of childbearing potential must be practicing at leastone or more the following methods of contraception during the study: intrauterinedevice (IUD), barrier method in combination with a spermicide, oral/hormonalcontraception or abstinence. Female patients of childbearing potential must have anegative pregnancy test prior to receiving study drug.
Written informed consent must be obtained from the subject prior to studyparticipation.
The subject is in good medical health or with chronic medical conditions which arecurrently stable.
No current abuse of alcohol or other substance.
The subject has a total score of 20 or more on the HARS or YBOCS at screening (for GADand OCD, respectively)
The subject has a Clinical Global Impression (CGI) Severity score of 4 or more atscreening.

Exclusion

Exclusion Criteria:

The subject meets DSM-IV criteria for an Axis I diagnosis (other than GAD or OCD) asthe primary diagnosis (i.e., schizophrenia, mood disorder, psychosis, anorexianervosa) as determined by the MINI.
The subject is clinically judged by the investigator to be at risk for suicide or isacutely suicidal as objectively measured by the MINI and MSE.
The subject is clinically judged by the investigator to be at risk for homicide or isacutely homicidal as objectively measured by the MINI and MSE.
The subject has a psychiatric condition that would require inpatient, or partialpsychiatric hospitalization.
Seizure disorders.
Significant history of medical disease (i.e. cardiovascular, hepatic (e.g. cirrhosis,hepatitis B or C) renal, gynecological, musculoskeletal, neurological,gastrointestinal, metabolic, hematological, endocrine, cancer with a metastaticpotential or progressive neurological disorders) which could impair reliableparticipation in the trial or necessitate the use of medication not allowed by thisprotocol.
The subject is pregnant, planning to become pregnant, or nursing. If a subject becomespregnant, she will be discontinued immediately and followed appropriately.
Concomitant therapy with another investigational drug, or participation in aninvestigational drug study within one month prior to entering this study.
Current psychotherapeutic treatment except for treatment with Specific ReuptakeInhibitor (SSRIs) medications which include: Fluoxetine (Prozac), Paroxetine (Paxil),Sertraline (Zoloft), Luvox (Fluvoxamine), and Citalopram. Potential subjects mayremain on one of the SSRI medications provided that he or she has been on a stabledose for at least 4 weeks prior to entering this study; this dose remains stablethroughout the remainder of this study; and it can be determined that this medicationis not exacerbating the anxiety symptoms.
History of poor compliance or in the Investigator's judgment patients any subjectwhose treatment as an outpatient would be clinically contraindicated
The subject has attempted suicide one or more times within the past twelve months
The subject has a Structured Hamilton Depression Rating Scale (SIGH-D) score above 38which suggests a moderate to severe clinical level of depressive symptoms

Study Design

May 01, 2005

January 31, 2008

Study Description

Several case reports and an open-label trial have reported efficacy of anti-glutamatergic medications for the treatment of OCD. In an open-label trial of riluzole, a glutamate release inhibitor, seven of 13 adult patients with OCD improved, and five were categorized as treatment responders. Another open trial found riluzole to be effective for four of six children with treatment-refractory OCD. N-acetylcysteine, an agent that likely attenuates glutamate neurotransmission, was effective as an augmentation in one patient with OCD. Two case reports described memantine treatment of OCD. Poyurovsky et al. reported improvement with memantine augmentation in one patient with treatment resistant OCD, while Pasquini and Biondi noted improvement in one OCD patient with checking compulsions but not in one with contamination obsessions. There have been no controlled or open-label trials of memantine in OCD reported thus far.

Few studies have examined the efficacy of anti-glutamatergic agents in GAD. In an open-label trial of riluzole treatment in 18 patients with GAD, twelve patients responded and eight achieved remission. A double-blind, controlled study found that LY354740, a metabotropic glutamate receptor 2/3 (mGlu2/3) agonist, was significantly more effective than placebo for GAD. No studies of memantine in GAD have been reported thus far. We hypothesized that treatment with memantine would result in significant symptom reduction in both OCD and GAD.

Connect with a study center

UCLA
Los Angeles, California 90095
United States
Site Not Available

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