The purpose of this study is to determine the safety and effectiveness of the drug memantine
for treating major depression.
Major depression is a serious public health concern that contributes to significant morbidity
and mortality. Despite the availability of a wide range of antidepressant drugs, a proportion
of patients with major depression fail to respond to first-line antidepressant treatment,
despite adequate dosage, duration, and compliance. Recent studies suggest that the
glutamatergic system may play a role in the pathophysiology and treatment of depression.
Memantine and other agents which reduce glutamatergic neurotransmission may represent a novel
class of antidepressants.
The study consists of three phases. In Phase 1, participants will be tapered off all
psychiatric medications over a 2-week washout period. In Phase 2, participants will be
randomly assigned to receive either memantine or placebo (an inactive pill) three times a day
for 8 weeks. Participants who do not respond to the treatment after 8 weeks will be taken off
the study and offered standard treatment. Weekly psychiatric evaluations will evaluate
treatment response. During Phase 2, participants who respond well to treatment will enter
Phase 3, a 16-week continuation phase of either memantine or placebo. Interviews will be
conducted every other week in the first month , then monthly thereafter.
Participants will have a physical examination, neuropsychological tests, and eye blink tests
at baseline and at the end of the study. Pulse, blood pressure, and blood samples will be
taken throughout the study. Participants will undergo an electrocardiogram as well as
positron emission tomography (PET) and magnetic resonance imaging (MRI) scans of the brain.