Memantine: A new mood-stabilizer for treatment-resistant Bipolar disorders

We have recently suggested that blockade of NMDA receptors by memantine could result in an antimanic and mood-stabilizing effect in treatment-resistant Bipolar Disorders (BD). Our group found suggestive evidence of mood-stabilizing actions in 40 BD patients in an unblinded, 12-month trial when added to stable, ongoing but inadequately effective standard treatments. Memantine as a monotherapy also has been reported to show beneficial effects in a few individual BD patients, including after discontinuation of lithium treatment. Finally, we published the results of a three-year naturalistic assessment of adding memantine to 30 treatment-resistant bipolar patients at the LucioBini Mood Disorder Center in Rome. In this unblinded trial, memantine appeared to add substantial long-term benefits, for both depressive and mania-like (mania, hypomania) morbidity, in outpatients who had responded consistently unsatisfactorily to standard treatments for more than 3 years, until memantine (20–30 mg/day) was added clinically to otherwise stable regimens for another 3 years, during which patients improved progressively. Memantine showed marked, statistically significant decreases of duration of illness (total, manic and depressive illness, on average –74.2%), symptom severity scores (CGI-BP; –63.1%), duration of new episodes (–56.3%), and recurrence frequency (episodes/year; –55.8%). These findings indicated impressive improvement in the duration and severity of both affective phases of the disorder, with a greater improvement of depression than mania, and evidence of decreased severity of mania indicated by shifting to hypomania. Subjects with previous rapid- (?4 episodes/year) or continuous-cycling were particularly improved. The possible mechanism of mood stabilizing effect of memantine will be discussed.