Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested, matched case-control study.
OBJECTIVE
This study investigated whether lithium, carbamazepine, and valproate increased the risk for hypothyroidism using Taiwan's National Health Insurance Dataset.


METHODS
The sample included 557 bipolar disorder patients with incident hypothyroidism first diagnosed between 1998 and 2004, and 2,228 sex-, age-, and index date-matched bipolar disorder patients without hypothyroidism from 1996-2004. We compared the use of lithium, carbamazepine, and valproate before the onset of hypothyroidism between the two groups using a conditional logistical regression model.


RESULTS
Compared with patients who had never used any of the three mood stabilizers, patients were more likely to have hypothyroidism if they only used carbamazepine [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.07-2.65]; or comedication of lithium and valproate (OR = 2.40; 95% CI: 1.70-3.40), lithium and carbamazepine (OR = 1.52; 95% CI: 1.10-2.08), and three mood stabilizers (OR = 2.34; 95% CI: 1.68-3.25). There was a dose-response relationship between the number of mood stabilizers and risk for hypothyroidism (OR = 1.34, 95% CI: 1.21-1.49) and a significant interaction between lithium and valproate on the risk for hypothyroidism (p = 0.020).


CONCLUSIONS
Our findings indicate that lithium, carbamazepine, and valproate may increase the risk for hypothyroidism, particularly if combined, and suggest regular monitoring of thyroid function and monotherapy of mood stabilizers for treating patients with bipolar disorders.
Gau
Churn-Shiouh
CS
Graduate Institute of Clinical Pharmacy, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. gaushufe@ntu.edu.tw
Chang
Ching-Jui
CJ
Tsai
Fang-Ju
FJ
Chao
Pei-Fong
PF
Gau
Susan Shur-Fen
SS
D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects* / Q000145:classification; D001714:Bipolar Disorder / Q000188:drug therapy*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009313:National Health Programs / Q000706:statistics & numerical data; D016017:Odds Ratio; D012307:Risk Factors; D013624:Taiwan
D018692:Antimanic Agents