Memantine in the management of affective recurrences of bipolar disorders after the discontinuation of long-term lithium treatment: three case histories

Abstract

Discontinuation of long-term lithium treatment leads to early and severe affective recurrences [Baldessarini et al. 1999], and to a bipolar disorder course more severe than that before lithium treatment with an increased risk of suicide [Post, 2012], which is often resistant not only to other mood stabilizers, but also to the reinstitution of lithium treatment at the prior effective serum lithium level [Post, 2012]. Unfortunately, the currently available lithium-alternative mood stabilizers are of limited (anticonvulsants) [Geddes et al. 2010; Kessing et al. 2011; Greil and Kleindiest, 1999], or questionable (atypical neuroleptics) [Goodwin et al. 2011] efficacy. We have recently provided clinical observations strongly suggesting that memantine, a noncompetitive N-methyl D-aspartate receptor antagonist, has a clinically relevant antimanic and a sustained mood-stabilizing effect in treatment-resistant bipolar disorder with excellent safety and tolerability [Koukopoulos et al. 2010, 2012; Sani et al. 2012; Serra et al. 2013]. More recently we have observed a long-lasting mood-stabilizing effect of memantine after lithium discontinuation in a bipolar I patient [Serra et al. 2013]. In order to evaluate further the effect of memantine in the prophylaxis of affective recurrences occurring after long-term lithium discontinuation, we administered the drug to three patients who had to discontinue lithium because of severe renal complications (two patients) or excessive tremor (one patient). These case histories confirm our previous observations, and suggest that memantine may be considered a useful lithium substitute to prevent the affective recurrences after lithium discontinuation. Case 1 Woman born in 1930, suffering from a bipolar II disorder with rapid cycling course. She has a family history of bipolar disorder. Her first affective episode was a depression in May 1979 (aged 49 years), followed by a hypomania until January 1980. She started lithium prophylaxis and had a very good response to lithium. In June 2009 lithium was gradually reduced to 150 mg every 2 days (serum lithium level 0.2 mmol/L) and then withdrawn because of renal impairment. After we had obtained the informed 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).