Association Between Lower Serum Free T₄ and Greater Mood Instability and Depression in Lithium-Maintained Bipolar Patients

OBJECTIVE: This investigation evaluated the relationship between changes in thyroid indices and mood stability during lithium and carbamazepine prophylaxis for bipolar disorder. METHOD: In the first 2 years, 30 patients with bipolar mood disorder were randomly assigned to 1 year of lithium and then 1 year of carbamazepine, or vice versa; in the third year, they received lithium plus carbamazepine. By stepwise regression analysis, the degree and timing of lithium- and carbamazepine-induced thyroid changes and their subsequent relationship to long-term mood stability were evaluated. RESULTS: During the lithium phase, there was a significant inverse relationship between morbidity and mean serum level of free T₄, i.e., a lower mean serum level of free T₄ was associated with more affective episodes and greater severity of depression as shown by the Beck Depression Inventory. During the carbamazepine phase, there was an inverse relationship between mean level of total T₄ and global severity rating. During the combination phase, no relationships between thyroid indices and clinical outcome were significant. CONCLUSIONS: In the lithium phase, a low level of free T₄ was associated with more affective episodes and greater severity of depression. Whether this mood instability is causally related to low free T₄ levels and whether it can be attenuated with T₄ replacement remain to be studied in a controlled setting.