Long-term treatment with supraphysiologic doses of levothyroxine in treatment-refractory mood disorders - A prospective study of cardiovascular tolerability

Background: To investigate long-term effects of adjunctive prophylactic treatment with supraphysiologic doses of levothyroxine (L-T4) on cardiovascular tolerability in 23 patients with treatment-refractory mood disorders. Methods: Starting point for a comprehensive cardiovascular assessment in patients was the indication for long-term maintenance treatment with L-T4 (mean dose 463 mcg/day). Prospective longitudinal assessment of the cardiovascular risk profile included in addition to a physical examination and blood pressure measurement, several technical investigations: resting electrocardiogram, transthoracic echocardiogram, cardiac stress test, and holter electrocardiogram. Statistical analysis was performed by linear mixed effects models (LMM) for evaluation of longitudinal changes in various heart measures. Results: During the mean observational period of 20.4 months none of the heart measures reached statistical significance in change over time. None of the assessed cardiac parameters of each single patient was in a range predictive for cardiac dysfunction. Limitations: Small sample size, no technical cardiac investigations prior to L-T4 initiation, no patient control group with mood disorders who did not receive L-T4. Conclusions: Results of this study indicated no increased risk for cardiovascular disorders during treatment with supraphysiologic L-T4 doses in patients with refractory mood disorders.