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).

see above

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