Treatment of imipramine-resistant recurrent depression: II. An open clinical trial of lithium augmentation.

Prior studies suggest that the addition of lithium salts may enhance treatment responses in depressions that have not responded to tricyclic antidepressants. The authors report on the efficacy of lithium augmentation in an open-label study of 20 outpatients with recurrent major depression who had not responded to greater than or equal to 12 weeks of treatment with imipramine (mean dosage = 256 mg/day) and psychotherapy. Only 1 patient (5%) responded during the first week of treatment, but the cumulative response rate increased to 65% during the 6-week clinical trial. Improvement in patients receiving lithium augmentation was significantly greater than the improvement observed in a historical control group of imipramine-resistant patients who received continued treatment with the imipramine-psychotherapy combination. The results support the usefulness of a 6-week trial of lithium augmentation in outpatients with resistant depression. It remains unclear whether the effectiveness of lithium augmentation is due to a true potentiation effect, a primary antidepressant effect by lithium, or a combination of both those factors.