Effect of abrupt change from standard to low serum levels of lithium: a reanalysis of double-blind lithium maintenance data.
OBJECTIVE
Growing evidence suggests that abrupt lithium discontinuation increases the risk of recurrence for patients with bipolar disorder. To assess the effect of abrupt change in lithium dose, the authors reanalyzed data from a previously reported, randomized, double-blind trial of standard- versus low-dose lithium for maintenance therapy in bipolar disorder.


METHODS
In the original study, serum lithium levels were obtained during a 2-month open stabilization period for 94 patients with bipolar disorder who were then randomly assigned to be maintained on a low (serum level=0.4-0.6 meq/liter) or a standard (0.8-1.0 meq/liter) level of lithium therapy. Patients were then followed for up to 182 weeks. This reanalysis examined the potential confounding influence of prerandomization lithium level and change in lithium level on the outcome of subjects assigned to a standard or low maintenance dose of lithium.


RESULTS
In a Cox proportional hazards model incorporating pre- and postrandomization lithium levels and the interaction of these factors, only the interaction term remained significantly associated with time to recurrence.


CONCLUSIONS
The findings indicate that change in serum lithium level may be a more powerful predictor of recurrence of bipolar disorder than the absolute assignment to a low or a standard dose of lithium and suggest that an abrupt decrease in lithium level should be avoided. This reanalysis did not directly address optimal maintenance lithium levels but raises questions about the original study's finding of superiority for lithium levels > or =0.8 meq/liter. The results underscore the importance of accounting for the possible confounding effects of changes in the intensity of pharmacotherapy in studies of maintenance therapies for bipolar disorder.
Perlis
Roy H
RH
Department of Psychiatry, Massachusetts General Hospital, 50 Staniford Street, Boston, MA 02114, USA. rperlis@partners.org
Sachs
Gary S
GS
Lafer
Beny
B
Otto
Michael W
MW
Faraone
Stephen V
SV
Kane
John M
JM
Rosenbaum
Jerrold F
JF
D000328:Adult; D001714:Bipolar Disorder / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015986:Confounding Factors, Epidemiologic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012107:Research Design / Q000706:statistics & numerical data; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D008094:Lithium