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.


METHODS
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.
Frye
M A
MA
Biological Psychiatry Branch, NIMH, NIH, Bethesda, MD 20892, USA.
Denicoff
K D
KD
Bryan
A L
AL
Smith-Jackson
E E
EE
Ali
S O
SO
Luckenbaugh
D
D
Leverich
G S
GS
Post
R M
RM
D000339:Affect / Q000187:drug effects; D001714:Bipolar Disorder / Q000097:blood / Q000517:prevention & control* / Q000523:psychology*; D002220:Carbamazepine / Q000494:pharmacology / Q000627:therapeutic use; D015897:Comorbidity; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced / Q000453:epidemiology; D015994:Incidence; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D012720:Severity of Illness Index; D013974:Thyroxine / Q000097:blood*; D016896:Treatment Outcome
D002220:Carbamazepine; D008094:Lithium; D013974:Thyroxine