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Thyroid function and psychiatric morbidity in patients with manic disorder receiving lithium therapy.

Euthyroid hyperthyroxinemia as a result of a transient increase in thyroid-stimulating hormone (TSH) levels may contribute to the development of manic disorder. Lithium has a potent short-term antithyroidal effect that may account for its antimanic action. The thyroid function and psychiatric morbidity of 46 adult patients with manic disorder were assessed prospectively before and 1 and 6 months after lithium treatment. At baseline, the free thyroxine level (FT4, 16.23 +/- 3.11 pmol/L) was at the high end of the normal range, whereas the free triiodothyronine (FT3, 4.24 +/- 0.65 pmol/L) and TSH (1.47 +/- 0.73 mIU/L) levels were within the normal range. All patients were clinically euthyroid, but five of them (11%) had elevated FT4 levels. Baseline FT3 and FT4 levels were positively correlated with past psychiatric morbidity. The FT4 level at baseline and after 1 month of treatment was positively correlated with scores on the Brief Psychiatric Rating Scale (p < 0.02) and negatively correlated with scores on the Global Assessment Scale (p < 0.005). During the first month of treatment, the reduction of FT3 and FT4 levels was significantly correlated with a decrease in psychiatric symptoms. By 6 months, the FT3 level was no longer significantly different from that at the baseline, but FT4 levels remained significantly lower. The TSH level increased progressively from baseline to 6 months. Multilevel models showed that FT4 and serum lithium levels were positively and negatively associated with psychiatric symptoms, respectively. The findings of the study lend support to the notion that euthyroid hyperthyroxinemia contributes to acute mania and suggest that lithium's short-term antimanic action may be mediated by its antithyroid effect.