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Outcome After Rapid vs Gradual Discontinuation of Lithium Treatment in Bipolar Disorders

Gianni L. Faedda, MD; Leonardo Tondo, MD; Ross J. Baldessarini, MD; Trisha Suppes, MD, PhD; Mauricio Tohen, MD, DrPH
Arch Gen Psychiatry. 1993;50(6):448-455. doi:10.1001/archpsyc.1993.01820180046005.
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Objective:  Withdrawal of bipolar mood disorder (BP-I) patients from prolonged, stable lithium maintenance has a high risk of early recurrence, particularly of mania. We thus compared risks of stopping lithium rapidly vs gradually.

Design:  Outpatients undergoing clinically determined discontinuation of lithium treatment at different rates were followed up prospectively to 5 years. Risks and timing of new episodes were analyzed.

Patients:  Subjects (N=64) with a DSM-III-R BP disorder, previously stable on lithium monotherapy for 18 to 120 months (mean, 3.6 years) were followed up clinically after discontinuing lithium (elected in prolonged wellbeing in 67%). None was unavailable for follow-up, and subtyping (BP-I or BP-II) remained stable.

Results:  Within 5 years, 75% had a recurrent episode; BP-I patients were 1.5-times less likely than BP-II to remain in remission. Polarity of first-recurrent and onset episodes was 80.8% concordant. Overall risk of a new episode of mania was significantly greater after rapid (<2) than gradual (2 to 4 weeks discontinuation (5-year hazard ratio=2.8); the difference in risk of depression was even greater hazard ratio=5.4). Recurrence rate was more elevated within months of rapid discontinuation (12month hazard ratio=5.4). Recurrence rate was more elevated within months of rapid discontinuation (12-month hazard ratio=4.3) than at later times (2 to 5 years), when courses of "survival" over time were nearly parallel in both discontinuation groups.

Conclusions:  Risk of early recurrence of BP disorder following discontinuation of lithium maintenance is elevated, but may be both predictable (timing and polarity) and modifiable by gradual discontinuation.


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