Update: Memantine as an Adjunct to Lamotrigine for Bipolar Depression
Memantine
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.
IV Scopolamine Brings About Rapid Onset Of Antidepressant Effects
Frankel and colleagues from the National Institute of Mental Health presented a randomized, placebo-controlled clinical trial of intravenous (IV) scopolamine for bipolar depression at the 9th International Conference on Bipolar Disorder (ICBD) in 2011. The same group of investigators previously showed that IV scopolamine was able to induce fast-acting antidepressant responses in those with unipolar major depression. This represents a new and independent study exclusively among patients with bipolar depression.
In the first phase of the study, three sessions of either IV scopolamine at 4 mcg/kg or a sham treatment were scheduled three to five days apart. In the second phase of the study, the patients were switched to the other treatment for three sessions. The results showed a rapid improvement in depression following the first session with scopolamine, more than occurred with the sham treatment. Hamilton Anxiety Rating scale (HAMA) scores also improved more on scopolamine than with the sham treatment, while Young Mania Rating Scores (YMRS) did not differ.
Editor’s note: As previously discussed in the BNN, scopolamine, an antagonist of acetylcholine muscarinic receptors, appears to exert rapid onset antidepressant effects in both unipolar and bipolar depression. When administered intravenously it takes its place with other rapidly acting antidepressant treatments, including IV ketamine, IV thyrotropin releasing hormone (TRH), and one night of sleep deprivation. The new data indicate that both unipolar and bipolar depression can respond rapidly (i.e. within a matter of hours) to certain treatments, even though most conventionally acting antidepressant modalities can take weeks to achieve maximum antidepressant effects. Read more
