A 10 Week Open-Label Pilot Study to Evaluate the Effectiveness and Safety of Memantine(Namenda) as Augmentation Therapy in Patients With Generalized Anxiety Disorder

Memantine is an FDA approved treatment which helps slow down the progression of Alzheimer's dementia.. It is felt that high glutamate levels associated with Alzheimer's dementia are toxic to neurons which ultimately die off causing the dementia process to continue. Memantine partially blocks the NMDA glutamate channels located on neurons in the brain. This way, if glutamate rises, its toxic activity is blunted and neurons tend to become less toxic and suffer less atrophy and death. Glutamate is felt to play a role in the development of anxiety as well. Glutamate is often in balance with another neurotransmitter, GABA. This GABA-glutamate balance (when GABA is low and Glutamate is normal to high) is also felt to play a role in the development of GAD or SAD. Low GABA and high glutamate levels (similar to the state of alcohol withdrawal) are implicated in causing anxiety symptoms. Sometimes, GABA-increasing sedative drugs, such as diazepam (Valium) are used to raise GABA activity to ward of anxiety symptoms and create a better balance between the stimulatory glutamate and inhibitory GABA. Given memantine's ability to lower glutamate levels, it may be able to also lower anxiety without the need for a sedative medication. Lowering glutamate this way, may allow a patient's own GABA concentrations to be more effective in lowering GAD or SAD symptoms. The usual treatment in initial treatment for anxiety is to use a serotonin neurotransmitter enhancing drug, such as paroxetine or escitalopram. These 'SSRI' drugs, unlike the sedatives noted above, do not have addiction potential and are safer to use. In the anxiety disorder population, only 30-70% of patients achieve full remission of anxiety symptoms when placed on SSRI monotherapy. The usual second-line choice is to treat with a serotonin-norepinephrine enhancing SNRI, such as venlafaxineXR in order to achieve remission. If resistance occurs to the SNRI, to promote full anxiety symptom relief, addition of a GABA enhancing-sedative (to raise GABA balance) to the SNRI is a reasonable polypharmacy strategy. Sedatives, like alprazolam, are addictive and considered third line agents now. The authors feel that memantine, given its ability to manipulate the GABA-glutamate balance by lowering glutamate without major side effects (weight gain, sexual problems, (ie SSRI/SNRI) nor addiction (ie sedatives) may be a reasonable add-on or augmentation strategy to better alleviate anxiety in SNRI or SSRI partial responders. This study is designed to evaluate generally or socially anxious patients who are only partially responsive to typical SNRI or SSRI anti-anxiety medication therapy. Patients who are less than 50% anxiety-alleviated on their SNRI medication will be asked to join the study and be placed on memantine as well. This type of add-on therapy is common in outpatient psychiatric care. This is a rater-blinded, patient open-label, non-placebo prospective pilot study, where all subjects will receive memantine for 10 weeks. This study would be the first to date in this treatment-resistant patient population, as the investigators will utilize the most comprehensive set of rating scales to date in order to best categorize patient responses in regards to anxiety with this drug.