Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression

Objective: Use of lithium to augment antidepressant medication has been sho wn to be beneficial in the acute treatment of depression. The authors exami ned the efficacy of lithium augmentation in the continuation treatment of u nipolar major depressive disorder. Method: Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study partici pated in a randomized, parallel-group, double-blind, placebo-controlled tri al of lithium augmentation during continuation treatment. After a 2-4-week stabilization period following remission, patients were randomly assigned t o receive either lithium or placebo for a 4-month period. Antidepressant me dication was continued throughout the study. Results: Relapses (including one suicide) occurred in seven (47%) of the 15 patients who received placebo in addition to antidepressants. None (0%) of the 14 patients who received lithium augmentation with antidepressants suf fered a relapse during the double-blind phase of the study. Five of the sev en relapsing patients in the placebo group developed a depressive episode, and the other two experienced a manic episode. Conclusions: Lithium augmentation in the continuation phase of treatment of unipolar major depressive disorder effectively protects patients against a relapse. Patients who respond to lithium augmentation should be maintained on lithium augmentation for a minimum of 6 months or even longer.