Predictors of relapse or recurrence in bipolar I disorder.
OBJECTIVE
Bipolar disorder represents a major public health concern and, despite treatment, is characterized by recurring episodes of mania, depression, or mixed states. Prevention of relapse or recurrence is a primary treatment objective in the management of the disorder. The objective of the current study was to identify predictors of relapse/recurrence in patients with bipolar I disorder treated with olanzapine, lithium, divalproex, or olanzapine plus divalproex/lithium.


METHODS
Data from four clinical trials studying the efficacy of olanzapine compared to placebo and active comparators (lithium, divalproex, olanzapine plus divalproex/lithium) for bipolar I disorder were pooled for this analysis. Patients achieving remission after pharmacological treatment and entering randomized double-blind maintenance phase for 44 to 72 weeks were included. Cox Proportional Hazard models and Kaplan-Meier analyses were used to determine predictors of relapse/recurrence for the pooled data and within each treatment group.


RESULTS
A total of 929 patients meeting the criteria for remission and followed by maintenance treatment were included in this analysis, and 427 patients (46.0%) experienced symptomatic relapse/recurrence during the follow-up period. A 21-item Hamilton Depression Rating Scale (HAMD-21) total score<4, gender, rapid cycling and treatment emerged as significant predictors of relapse/recurrence and may be generalized to treatment with olanzapine and to some extent to treatment with lithium and divalproex. The results on treatment-specific predictors of relapse/recurrence are considered to be exploratory and no adjustments were made for multiple comparisons.


CONCLUSIONS
The major findings from this study suggest that a HAMD-21 total score<4 may be a better predictor of maintenance of remission in bipolar I patients than HAMD-21 total score<8. The prophylactic effect of olanzapine, lithium, divalproex, olanzapine plus divalproex or lithium, and placebo was assessed and baseline predictors of relapse/recurrence were identified.
Eli Lilly and Company, Indianapolis, IN 46285, USA.
Elisabeth K
EK
Degenhardt
Jennifer L
JL
Gatz
Jayanthi
J
Jacob
Mauricio
M
Tohen
D000293:Adolescent; D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011379:Prognosis; D012008:Recurrence; D014635:Valproic Acid / Q000627:therapeutic use
D018692:Antimanic Agents; D001569:Benzodiazepines; D014635:Valproic Acid; D008094:Lithium; D000077152:Olanzapine