MEMANTINE IN TREATMENT-RESISTANT BIPOLAR DISORDER: CLINICAL EVIDENCES
Growing evidences show that memantine might be effective at preventing recurrences of both phases of bipolar disorder and in reducing the manic-like symptomatology associated with several neurological and psychiatric conditions[11,12,91]. Memantine monotherapy was reported to show evidence of antimanic effects at well-tolerated daily doses (20-50 mg) in a three-week open-label trial in 33 acutely manic patients[92]. Our group found suggestive evidence of mood-stabilizing actions in 40 BD patients in two unblinded, 6 and 12-mo open label trials when memantine was added to stable, ongoing but inadequately effective treatments[93,94]. Memantine as a monotherapy also has been reported to show beneficial effects in a few individual patients with bipolar disorder, including after discontinuation of lithium treatment[95-98]. Another short- term study found memantine to be more effective than placebo when added to lamotrigine for four weeks to treat acute bipolar depression in a randomized, controlled trial, but this effect was no longer significant at 8 wk[99]. A recent 12-wk trial found little overall difference in effects of small doses of memantine (5 mg/d; n = 62) vs placebo added to valproate in bipolar II disorder patients for 12 wk[100]. Finally, we just reported the results of a three-year naturalistic study of adding memantine to 30 treatment- resistant bipolar patients[91]. In this study memantine showed a long-term and progressive ability to prevent depressive and mania/hypomania recurrences, in patients who had been resistant to standard treatments for more than 3 years. Memantine decreases the duration of illness, the duration of new episodes, recurrence frequency and symptomatology severity.
Finally, it has been recently reported that memantine improves cognitive dysfunctions and increases hippocampal volume in euthymic bipolar patients[101].