Ma. Frye et al., Association between lower serum free T-4 and greater mood instability and depression in lithium-maintained bipolar patients, AM J PSYCHI, 156(12), 1999, pp. 1909-1914
Objective: This investigation evaluated the relationship between changes in
thyroid indices and mood stability during lithium and carbamazepine prophy
laxis 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 li
thium plus carbamazepine. By stepwise regression analysis, the degree and t
iming of lithium- and carbamazepine-induced thyroid changes and their subse
quent relationship to long-term mood stability were evaluated. Results: Dur
ing the lithium phase, there was a significant inverse relationship between
morbidity and mean serum level of free T-4, i.e., a lower mean serum level
of free T-4 was associated with more affective episodes and greater severi
ty of depression as shown by the Beck Depression Inventory. During the carb
amazepine phase, there was an inverse relationship between mean level of to
tal T-4 and global severity rating. During the combination phase, no relati
onships between thyroid indices and clinical outcome were significant. Conc
lusions: In the lithium phase, a low level of free T-4 was associated with
more affective episodes and greater severity of depression. Whether this mo
od instability is causally related to low free T-4 levels and whether it ca
n be attenuated with T-4 replacement remain to be studied in a controlled s
etting.