Liothyronine (T3) for Bipolar Depression

Bipolar affective disorder is a debilitating illness, and is characterized by depression
episodes that dominates the longitudinal course and are most difficult to treat. Controlled
trials with monotherapy mood stabilizers such as lithium and valproate show little to no
efficacy and antidepressants may offer no additional efficacy. Recently there has been a
growing interest in the use of quetiapine in bipolar depression. However, a successful
treatment may take up to 8 weeks, and full remission is achieved in only 50% of patients.
Thyroid hormone augmentation strategies have been used in unipolar depression with good
results, but there is a paucity of its efficacy in bipolar depression (BD). To our knowledge
there are no controlled studies regarding the efficacy of thyroid augmentation in BD. The
present study proposes to evaluate the efficacy of T3 as an augmentation to treatment as
usual in the treatment of BD. We plan to enroll patients with bipolar disorder I or II who
are currently presenting with depressive symptoms. Patients will be randomized to 2 groups -
liothyronine or placebo Results will provide information on the possible role of thyroid
hormone augmentation in the treatment of patients with bipolar depression, and may
contribute to alleviate the burden of this disabling condition.

Inclusion Criteria:

1. Age 18-65;

2. DSM-IV diagnosis of BP I or BP II as per SCID;

3. Currently presenting with at least moderate levels of depression (HAM-D > 15;

4. Patient has to be on stable dose of at least one mood stabilizer (lithium, valproate,
carbamazepine, lamotrigine, second generation antipsychotics) for at least 4 weeks as
per history;

5. Antidepressants and/or additional mood stabilizers are allowed, but dose should be
stable for at least 2 weeks;

Exclusion Criteria:

1. Evidence of acute mania or hypomania (as measured by CARS-M > 7);

2. Abnormal (outside of lab normal range) thyroid function tests;

3. Current thyroid hormone treatment;

4. Any medical condition considered a contraindication for treatment with T3 (i.e.
history of myocardial infarction, cardiac arrhythmia, severe cardiac insufficiency,
Autoimmune Thyroid Disease /Hashimoto's Thyroiditis as determined by anti-thyroid
antibody testing, previous or current thyroid adenoma, hyperthyroidism);

5. EKG showing rhythm other than sinus or repolarization phase abnormalities;

6. Current alcohol or substance abuse or dependence in past month as per SCID;

7. Score of 3 or more on the suicide item of the HAM-D;

8. Females who are pregnant, breastfeeding, or of childbearing age and not using
adequate birth control.