Memantine Treatment for Obsessive-compulsive Disorder and Generalized Anxiety Disorder

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT00674219
• Collaborator: Saban Family Foundation (Other)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Obsessive-Compulsive Disorder; Generalized Anxiety Disorder	Drug: Memantine	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Differential Efficacy of Memantine for Obsessive-compulsive Disorder vs. Generalized Anxiety Disorder: an Open-label Trial
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: OCD group OCD group - received 12 weeks of open-label memantine 10 mg twice daily, as either mono therapy or augmentation of their existing medication.	Drug: Memantine; Namenda 10mg BID for 12 weeks; Other Names: Namenda
Active Comparator: GAD group GAD group - received 12 weeks of open-label memantine 10 mg twice daily, as either mono therapy or augmentation of their existing medication.	Drug: Memantine; Namenda 10mg BID for 12 weeks; Other Names: Namenda

Outcome Measures

Primary Outcome Measures

1. Psychometric Scores [Baseline, 12 weeks]

   Participants in the OCD group were rated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), a standard measure of obsessive-compulsive disorder (OCD) severity in pharmacotherapy studies. It is administered by a trained rater. It comprises 10 items assessing OCD symptoms (e.g. time spent, degree of control, severity). Each item is scored on a scale from 0 (not present) to 4 (severe) [total score range = 0-40] over the previous week. The higher the number on the Y-BOCS, the more severe the symptoms. Participants in the GAD group were rated using the Hamilton Anxiety Rating Scale (HARS), a standard measure of anxiety severity in pharmacotherapy studies. It is administered by a trained rater. It comprises 14 items assessing anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 Obsessive Compulsive Disorder as determined by the MINI.

• Sexually active female patients of childbearing potential must be practicing at least one or more the following methods of contraception during the study: intrauterine device (IUD), barrier method in combination with a spermicide, oral/hormonal contraception or abstinence. Female patients of childbearing potential must have a negative pregnancy test prior to receiving study drug.

• Written informed consent must be obtained from the subject prior to study participation.

• The subject is in good medical health or with chronic medical conditions which are currently 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 GAD and OCD, respectively)

• The subject has a Clinical Global Impression (CGI) Severity score of 4 or more at screening.

Exclusion Criteria:

• The subject meets DSM-IV criteria for an Axis I diagnosis (other than GAD or OCD) as the primary diagnosis (i.e., schizophrenia, mood disorder, psychosis, anorexia nervosa) as determined by the MINI.

• The subject is clinically judged by the investigator to be at risk for suicide or is acutely suicidal as objectively measured by the MINI and MSE.

• The subject is clinically judged by the investigator to be at risk for homicide or is acutely homicidal as objectively measured by the MINI and MSE.

• The subject has a psychiatric condition that would require inpatient, or partial psychiatric 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 metastatic potential or progressive neurological disorders) which could impair reliable participation in the trial or necessitate the use of medication not allowed by this protocol.

• The subject is pregnant, planning to become pregnant, or nursing. If a subject becomes pregnant, she will be discontinued immediately and followed appropriately.

• Concomitant therapy with another investigational drug, or participation in an investigational drug study within one month prior to entering this study.

• Current psychotherapeutic treatment except for treatment with Specific Reuptake Inhibitor (SSRIs) medications which include: Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft), Luvox (Fluvoxamine), and Citalopram. Potential subjects may remain on one of the SSRI medications provided that he or she has been on a stable dose for at least 4 weeks prior to entering this study; this dose remains stable throughout the remainder of this study; and it can be determined that this medication is not exacerbating the anxiety symptoms.

• History of poor compliance or in the Investigator's judgment patients any subject whose 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 38 which suggests a moderate to severe clinical level of depressive symptoms

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States	90095

Sponsors and Collaborators

• University of California, Los Angeles
• Saban Family Foundation

Investigators

• Principal Investigator: Alexander Bystritsky, MD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexander Bystritsky, Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00674219
• Other Study ID Numbers: 04-08-063-03
• First Posted: May 7, 2008
• Last Update Posted: May 10, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Alexander Bystritsky, Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles: Obsessive-compulsive disorder; Generalized anxiety disorder; Memantine; Namenda
• Additional relevant MeSH terms: Disease; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Memantine

Study Results

Participant Flow

Recruitment Details	Participants were recruited during 2007-2008 from the Anxiety Disorders Program at UCLA.

Arm/Group Title	OCD Group	GAD Group
Arm/Group Description	Persons meeting inclusion criteria for a diagnosis of obsessive-compulsive disorder.	Persons meeting inclusion criteria for a diagnosis of generalized anxiety disorder.
Period Title: Overall Study
STARTED	10	7
COMPLETED	10	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	OCD Group	GAD Group	Total
Arm/Group Description	Persons meeting inclusion criteria for a diagnosis of obsessive-compulsive disorder	Persons meeting inclusion criteria for a diagnosis of generalized anxiety disorder	Total of all reporting groups
Overall Participants	10	7	17
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	38.6	37	37.9
Sex: Female, Male (Count of Participants)
Female	6 60%	5 71.4%	11 64.7%
Male	4 40%	2 28.6%	6 35.3%
Diagnosis of OCD or GAD (participants) [Number]
Number [participants]	10 100%	7 100%	17 100%

Outcome Measures

1. Primary Outcome

Title	Psychometric Scores
Description	Participants in the OCD group were rated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), a standard measure of obsessive-compulsive disorder (OCD) severity in pharmacotherapy studies. It is administered by a trained rater. It comprises 10 items assessing OCD symptoms (e.g. time spent, degree of control, severity). Each item is scored on a scale from 0 (not present) to 4 (severe) [total score range = 0-40] over the previous week. The higher the number on the Y-BOCS, the more severe the symptoms. Participants in the GAD group were rated using the Hamilton Anxiety Rating Scale (HARS), a standard measure of anxiety severity in pharmacotherapy studies. It is administered by a trained rater. It comprises 14 items assessing anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	OCD Group	GAD Group
Arm/Group Description	Persons meeting inclusion criteria for a diagnosis of OCD.	Persons meeting inclusion criteria for a diagnosis of GAD.
Measure Participants	10	7
12 weeks	16.4 (13.6)	18.86 (4.14)
Baseline	27.6 (4.4)	24.3 (1.7)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	OCD Group		GAD Group
Arm/Group Description	OCD group - received 12 weeks of open-label memantine 10 mg twice daily, as either mono therapy or augmentation of their existing medication. Memantine: Namenda 10mg BID for 12 weeks		GAD group - received 12 weeks of open-label memantine 10 mg twice daily, as either mono therapy or augmentation of their existing medication. Memantine: Namenda 10mg BID for 12 weeks
All Cause Mortality
	OCD Group		GAD Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/7 (0%)
Serious Adverse Events
	OCD Group		GAD Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	OCD Group		GAD Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		3/7 (42.9%)
Nervous system disorders
dizziness	3/10 (30%)	3	3/7 (42.9%)	3
Somnolence	2/10 (20%)	3	1/7 (14.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.