BACKGROUND: Gradual discontinuation of lithium may reduce high risk of early morbidity in bipolar disorder patients discontinuing successful long-term maintenance on lithium, but previous small samples have limited analyses of subgroups. METHOD: DSM-IV bipolar disorder patients (N = 161) were pooled from similar samples maintained on lithium for 4.2 +/- 3.1 years. Effects of discontinuing treatment abruptly (1-14 days) or gradually (15-30 days) were compared by survival analysis in clinically closely similar groups. RESULTS: After gradual versus rapid discontinuation, the overall median time to recurrence +/- SE differed by 5.0-fold (20.0 +/- 5.8 vs. 4.0 +/- 0.7 months; p < .0001). After rapid discontinuation, the median time in remission was 2.3 times shorter than the mean cycling interval before lithium (6.3 vs. 14.6 months; p < .0001). The proportion of subjects falling ill/month (recurrence rate) was much higher in the first year after rapid discontinuation (6.5% vs. 2.3%), but similar thereafter (0.4% vs. 0.6%); patients remained stable for 3 years when off lithium treatment 20 times more frequently after gradual than rapid discontinuation (37% vs. 1.8%; p < .0001). Ratios of median survival times after gradual/rapid lithium discontinuation were similar for a first recurrence of mania and depression (4.4 vs. 3.4-fold), insignificantly higher (34%) with rapid or continuous cycling before lithium, and greater in Type II than Type I disorder (9.8- vs. 4.0-fold). The polarity of first off-lithium and first lifetime episodes matched in 70% of cases. CONCLUSION: These pooled results strengthen the concept or a pharmacodynamic stress factor in early relapse after stopping lithium maintenance and support the conclusion that early recurrence risk can be minimized by discontinuing maintenance treatment gradually in both Type I and II bipolar disorders.
BACKGROUND: Gradual discontinuation of lithium may reduce high risk of early morbidity in bipolar disorderpatients discontinuing successful long-term maintenance on lithium, but previous small samples have limited analyses of subgroups. METHOD: DSM-IV bipolar disorderpatients (N = 161) were pooled from similar samples maintained on lithium for 4.2 +/- 3.1 years. Effects of discontinuing treatment abruptly (1-14 days) or gradually (15-30 days) were compared by survival analysis in clinically closely similar groups. RESULTS: After gradual versus rapid discontinuation, the overall median time to recurrence +/- SE differed by 5.0-fold (20.0 +/- 5.8 vs. 4.0 +/- 0.7 months; p < .0001). After rapid discontinuation, the median time in remission was 2.3 times shorter than the mean cycling interval before lithium (6.3 vs. 14.6 months; p < .0001). The proportion of subjects falling ill/month (recurrence rate) was much higher in the first year after rapid discontinuation (6.5% vs. 2.3%), but similar thereafter (0.4% vs. 0.6%); patients remained stable for 3 years when off lithium treatment 20 times more frequently after gradual than rapid discontinuation (37% vs. 1.8%; p < .0001). Ratios of median survival times after gradual/rapid lithium discontinuation were similar for a first recurrence of mania and depression (4.4 vs. 3.4-fold), insignificantly higher (34%) with rapid or continuous cycling before lithium, and greater in Type II than Type I disorder (9.8- vs. 4.0-fold). The polarity of first off-lithium and first lifetime episodes matched in 70% of cases. CONCLUSION: These pooled results strengthen the concept or a pharmacodynamic stress factor in early relapse after stopping lithium maintenance and support the conclusion that early recurrence risk can be minimized by discontinuing maintenance treatment gradually in both Type I and II bipolar disorders.
Authors: Maria A Oquendo; Hanga C Galfalvy; Dianne Currier; Michael F Grunebaum; Leo Sher; Gregory M Sullivan; Ainsley K Burke; Jill Harkavy-Friedman; M Elizabeth Sublette; Ramin V Parsey; J John Mann Journal: Am J Psychiatry Date: 2011-07-18 Impact factor: 18.112
Authors: Alexander C Tsai; Nicholas Z Rosenlicht; Jon N Jureidini; Peter I Parry; Glen I Spielmans; David Healy Journal: PLoS Med Date: 2011-05-03 Impact factor: 11.069
Authors: Eric G Smith; Karen L Austin; Hyungjin Myra Kim; Donald R Miller; Susan V Eisen; Cindy L Christiansen; Amy M Kilbourne; Brian C Sauer; John F McCarthy; Marcia Valenstein Journal: BMC Psychiatry Date: 2014-12-17 Impact factor: 3.630