2 mmol/L) and then withdrawn because of renal impairment. After we had obtained the informed FK506 clinical trial written consent, she was put on 20 mg/day memantine and lamotrigine (250 mg/day). She started with rapid cycling recurrences until May 2010. Since then she has been well and stable on memantine 20 mg/day, lamotrigine 250 mg/day and lithium 150 mg every 2 days (lithium

serum level 0.2 mmol/L). Case 2 Woman born in 1934, suffering from a bipolar II disorder with rapid cycling course. She has a family history of mood disorder. Inhibitors,research,lifescience,medical She had her first depressive episode in 1985. In 2000 she started having hypomanias and depressions with a rapid cycling course. Then she was totally stabilized with lithium therapy. In February 2004 lithium

Inhibitors,research,lifescience,medical was reduced because of renal impairment and valproic acid was added at 600–900 mg/day. In November 2008 the patient started having a rapid recurrence of hypomanic and depressive episodes and in November 2009 lithium had to be finally withdrawn because of the worsening of renal impairment. In March 2010, after we had obtained the informed written consent, memantine Inhibitors,research,lifescience,medical 20 mg/day was added to valproic acid. She had a depressive episode milder than the previous one. Currently mood oscillations persist but are much milder than those she had before lithium treatment and before memantine. Case 3 Woman born in 1937, retired teacher, suffering from a bipolar II disorder with rapid cycling course. Her mood disorder started in 2006 (aged 68 years) with a major depressive episode. Subsequently her unipolar depression converted to a bipolar Inhibitors,research,lifescience,medical type II disorder with a rapid cycling course. In June 2009 she started treatment with lithium 300 mg/day (serum lithium level 0.4 mmol/L), lamotrigine 200 mg/day and clonazepam 0.5 mg/day. Although maintaining a rapid cycling course, her mood episodes became milder,

but she started suffering from a disabling tremor due to lithium, and she had a severe skin reaction due to lamotrigine (rapidly discontinued). Inhibitors,research,lifescience,medical After we had obtained written informed consent, memantine was added and titrated to 20 mg/day within a week. The rapid course was stopped. She had another mild euphoria immediately interrupted by adding valproic acid (600 mg/day). In March 2011 lithium was gradually discontinued because of disabling tremors. Since June 2011 she has been completely euthymic with memantine 20 mg/day and valproic acid 450 mg/day. Discussion These observations suggest that memantine could effectively replace lithium Resminostat and stabilize the course of bipolar disorder in patients who discontinue long-term lithium treatment. In case 1 we added memantine and lamotrigine to treat rapid recurrences triggered by lithium discontinuation, which led to severe recurrences that had to be treated with electroconvulsive therapy. This clinical condition is usually resistant to conventional mood stabilizers, including the reinstitution of lithium [Post, 2012].