Carbamazepine augmentation in lithium refractory bipolar patients: a prospective study on long-term prophylactic effectiveness

Twenty-two patients affected by bipolar or schizoaffective disorder, in whom carbamazepine was added to lithium after recurrence when on maintenance with lithium alone, were followed up prospectively for 2 to 13 years. The number of episodes, hospitalizations, and cumulative affective morbidity was markedly reduced after carbamazepine augmentation. Seventeen patients presented a better course during combined treatment than during lithium alone, and of these 15 had no further recurrences. Four patients did not appear to improve after carbamazepine augmentation, whereas one featured reemergence of affective episodes after having derived satisfactory benefit from combination for 7 years (delayed tolerance). Carbamazepine augmentation was associated with a reduction of lithium doses in some patients, including a subgroup who had not tolerated lithium at usual therapeutic levels. Carbamazepine significantly reduced serum thyrotropin concentrations, which were abnormally high in approximately one half of patients when on lithium alone. Total serum thyroxine concentrations were also decreased after carbamazepine augmentation, but free thyroid hormone concentrations did not change. Other significant carbamazepine-induced changes in laboratory tests included increases in total cholesterol concentrations and decreases in white blood cell counts.