Update: Memantine as an Adjunct to Lamotrigine for Bipolar Depression

Memantine (Namenda), which is approved by the Federal Drug Administration (FDA) for use in Alzheimer’s Dementia, is increasingly being used for other conditions. Some doctors prescribe memantine for hyperactivity and attention problems in attention deficit hyperactivity disorder (ADHD), for obsessive compulsive disorder (OCD), and most recently as an adjunct to lamotrigine in bipolar depression. We wrote about the findings of Amit Anand et al. on the use of memantine and lamotrigine in January. These findings have just been published in Bipolar Disorders. The study indicates that the combination of lamotrigine with memantine brought about a rapid onset and greater magnitude of antidepressant effects than the combination of lamotrigine and placebo. The initial dose of memantine was 5mg/day, which was increased to 20mg/day during the study.

Editor’s Note: The potential mechanism of this effect makes sense. Lamotrigine decreases release of glutamate, and memantine blocks glutamate’s actions at the NMDA receptor. Thus the two together would more efficiently decrease glutamate’s effects.

It is possible that memantine could be effective without effecting the normal functions of glutamate. The drug blocks NMDA glutamate receptors that are situated away from the synapse, while allowing NMDA glutamate receptors at the synapse to fulfill their normal functions that support learning and memory. The blocking of only those receptors outside the synapse (extra-synaptic) could explain why memantine has relatively few side effects.

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