COMPARATIVE PROPHYLACTIC EFFICACY OF LITHIUM, CARBAMAZEPINE, AND THE COMBINATION IN BIPOLAR DISORDER

Background: We compared the prophylactic efficacy of lithium, carbamaz epine, and the combination and identified possible clinical markers of response. Method: Fifty-two outpatients who met DSM-III-R criteria fo r bipolar illness were randomly assigned in a double-blind design fur an intended I year of treatment with lithium or carbamazepine, a cross over to the opposite drug in the second gear, and then a third year on the combination, Patients received monthly detailed evaluations, and daily life chart ratings of the degree of functional incapacity associ ated with mania or depression were completed. Results: For evaluable p atients: 13 (31.0%) of 42 failed to complete a full year of lithium th erapy owing to lack of efficacy, and 2 dropped our because of side eff ects, 13 (37.1%) of 35 withdrew from carbamazepine within the first ye ar owing to lack of efficacy, and 10 dropped out because of side effec ts (9 of the 10 had a rash; 7 (24.1%) of 29 withdrew from the combinat ion therapy owing to lack of efficacy. The percentage of the evaluable patients who had marked or moderate improvement on the Clinical Globa l Impressions scale was 33.3% on lithium, 11.4% on carbamazepine, and 55.2% on the combination treatment, which was not significantly differ ent, By a variety of measures, lithium was more effective than carbama zepine in the prophylaxis of mania, Patients with a past history of ra pid cycling did poorly on monotherapy (28.0% responded to lithium; 19. 0% responded to carbamazepine), but significantly better on the combin ation (56.3%, p < .05). Conclusion: These prospective, randomized data suggest a high incidence of inadequate response to either mood stabil izer or their combination despite use of adjunctive agents as needed, Additional novel treatment regimens are needed to better decrease affe ctive morbidity in large numbers of bipolar outpatients.