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
Condition: General Anxiety Disorder, Social Anxiety Disorder
MeSH terms: Anxiety Disorders; Phobia, Social
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is being conducted to evaluate the safety and effectiveness of memantine Add-On
      treatment of patients who are currently taking an SNRI or SSRI and who remain anxious and
      symptomatic despite treatment.

      Secondary objectives of this study are:

      •-to evaluate if there is an improvement in disability levels following memantine dosing

      -to evaluate if there is an improvement in sleep quality following memantine dosing
    

Detailed description: 
      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.
    

Intervention name(s): Namenda/Memantine
Intervention type(s): Drug
Intervention description(s): 5mg tablets, 1-4 tabs by mouth per day
Intervention MeSH terms: Memantine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Anxiety, SNRI, SSRI,GAD,SAD