Clinical Trial of Memantine for Major Depression

Summary

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.

Timeline

Start

2002-06

Primary completion

—

Completion

2005-03

Publications

• Background Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993 Nov;150(11):1731-3. doi: 10.1176/ajp.150.11.1731.
• Background Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000 Feb 15;47(4):305-13. doi: 10.1016/s0006-3223(99)00159-6.
• Background Ambrozi L, Danielczyk W. Treatment of impaired cerebral function in psychogeriatric patients with memantine--results of a phase II double-blind study. Pharmacopsychiatry. 1988 May;21(3):144-6. doi: 10.1055/s-2007-1014666.
• Lepow L, Luckenbaugh DA, Park L, Henter ID, Zarate CA Jr. Case series: Antidepressant effects of low-affinity and low-trapping NMDA receptor antagonists did not predict response to ketamine in seven subjects. J Psychiatr Res. 2017 Mar;86:55-57. doi: 10.1016/j.jpsychires.2016.10.023. Epub 2016 Nov 22. No abstract available.

Drugs

Indications