General Anxiety Disorder, Social Anxiety Disorder Clinical Trial
Official title:
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 (GAD) or Social Anxiety Disorder (SAD), Who Are Only Partial Responders to Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRI's) or Selective Serotonin Reuptake Inhibitors (SSRI's).
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
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.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment