It may be used when there is an impaired conversion of T4 to T3 in peripheral tissues. The dose of liothyronine for hypothyroidism is a lower amount than levothyroxine due it being a higher concentrated synthetic medication. About 25 μg of liothyronine is equivalent to 100 μg of levothyroxine. It may also be used for myxedema coma because of its quicker onset of action when compared to levothyroxine.

Adding liothyronine to tricyclic antidepressants appears useful, especially in women. An algorithm developed from the STAR*D trial recommends liothyronine as an option when people have failed two antidepressant medications.

Use for the treatment of obesity is not recommended.

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