Memantine Augmentation in Treatment-Resistant Adults With Obsessive-Compulsive Disorder

Open -Label Trial on the Effects of Memantine in Adults With Obsessive-Compulsive Disorder After a Single Ketamine Infusion

Obsessive-compulsive disorder (OCD) is a common psychiatric illness that affects up to 2-3% of the population. People with OCD experience anxiety-provoking, intrusive thoughts, known as obsessions, and feel compelled to perform repetitive behaviors, or compulsions. The only medications proven effective for OCD are serotonin reuptake inhibitors (SRIs), but even with SRI treatment, most patients continue to experience significant OCD symptoms, impaired functioning, and diminished quality of life. Recent evidence suggest that a different neurotransmitter, glutamate, may contribute to the symptoms in OCD. Medications that target glutamate hold promise for ameliorating symptoms for those patients continuing to suffer from OCD. In this study the investigators are recruiting patients to receive the drug memantine, which is thought to modulate the neurotransmitter glutamate, added to whatever other OCD medications they are taking.

Open label memantine will be titrated in 5mg increments weekly to target dose of 10mg po bid for up to 6 weeks. Memantine will be continued to 12 weeks in those with treatment response,13 either previous response to ketamine (≥ 35% Y-BOCS reduction 1 week after IV ketamine) or current response to memantine (≥ 35% Y-BOCS reduction from pre- to post-6 weeks of memantine).

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Drug: Memantine

Detailed Description

see above

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-65 years old
2. Primary Diagnosis of OCD
3. Physically healthy and females must be using effective contraception
4. At lease moderate OCD symptoms (Yale-Brown Obsessive-Compulsive Scale [YBOCS]score greater or equal to 16 prior to entering trial)
5. Able to provide consent

6. May be on or off selective reuptake inhibitor (SRI) medications

   1. Patients on an SRI medication will be included if the dose is stable and adequate (or if they don't want to increase their dose [e.g. side effects] and have a history of prior SRI or CBT treatment meeting criteria for adequate trial)
   2. Patients not on an SRI medication will be included if they they have failed at least 1 prior trial of standard OCD treatment (e.g. SRIs or CBT)

Exclusion Criteria:

1. Ongoing treatment with memantine
2. Patients planning to start CBT during the study period or those who have started CBT within 8 weeks prior to study enrollment
3. Presence of psychotic symptoms or lifetime history of schizophrenia, bipolar disorder, or other psychotic disorder.
4. Current major depressive disorder (patients must be free of the disorder for three months prior to enrollment). Patients will be excluded if they are moderately to severely depressed, but if they are mildly to moderately depressed they will be included (Hamilton Depression Rating Scale must be <18).
5. Judged clinically to be at risk of suicide (suicidal ideation, severe depression, or other factors).
6. Current eating disorder
7. Females who are pregnant or nursing
8. Severe renal insufficiency, severe hepatic impairment, or seizure disorder.
9. Documented history of hypersensitivity or intolerance to memantine.
10. Concomitant use of trimethoprim, N-methyl-D-aspartate receptor medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Memantine; Open label memantine titrated in 5mg increments weekly to target dose of 10mg po bid for up to 6 weeks. Memantine was continued to 12 weeks in those with treatment response,13 either previous response to ketamine (≥ 35% Y-BOCS reduction 1 week after IV ketamine) or current response to memantine (≥ 35% Y-BOCS reduction from pre- to post-6 weeks of memantine).	Drug: Memantine; Open label memantine titrated in 5mg increments weekly to target dose of 10mg po bid for up to 6 weeks. Memantine was continued to 12 weeks in those with treatment response,13 either previous response to ketamine (≥ 35% Y-BOCS reduction 1 week after IV ketamine) or current response to memantine (≥ 35% Y-BOCS reduction from pre- to post-6 weeks of memantine).; Other Names: Namenda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Who Met and Exceeded Response Criteria of Yale-Brown Obsessive-Compulsive Scale.	Patients given YBOCS (Yale Brown Obsessive-Compulsive Scale), a gold standard measure of obsessions and compulsions. For the YBOCS the minimum units are 0 and Maximum units on the total scale are 40. The higher the number on the YBOCS, the more severe the symptoms. Response was defined as at least a 35% reduction on the YBOCS.	Baseline and 6 weeks

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Investigators: Principal Investigator: Helen B Simpson, MD, PhD, NYSPI-Columbia

Publications and helpful links

General Publications

• Rodriguez CI, Levinson A, Zwerling J, Vermes D, Simpson HB. Open-Label trial on the effects of memantine in adults with obsessive-compulsive disorder after a single ketamine infusion. J Clin Psychiatry. 2016 May;77(5):688-9. doi: 10.4088/JCP.15l10318. No abstract available.

Helpful Links

• Columbia University Obsessive-Compulsive Disorder Research Clinic
• Rodriguez Lab - Stanford University

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 10, 2009
• First Submitted That Met QC Criteria: August 10, 2009
• First Posted (Estimate): August 11, 2009

Study Record Updates

• Last Update Posted (Actual): June 21, 2017
• Last Update Submitted That Met QC Criteria: June 20, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: OCD
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: 6924R/5972

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No