Official Title: “Randomized Double-Blind Trial of Liothyronine (T3) Augmentation to Quetiapine vs Placebo Augmentation to Quetiapine for the Treatment of Bipolar Depression”

This study evaluates the efficacy of the thyroid hormone T3 for depression in patients with bipolar disorder. In this study patients will be treated with quetiapine, an approved treatment for bipolar depression, and will be randomized to receive T3 or placebo.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: July 2010

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 strategy to quetiapine in the treatment of BD. We plan to enroll patients with bipolar disorder I or II who are currently taking valproate or lithium plus quetiapine for at least 4 weeks for treatment of a current depressive episode. Patients will be randomized to 2 groups - quetiapine plus liothyronine or quetiapine plus placebo Results will provide information on the possible role of thyroid hormone augmentation in the treatment of patients with bipolar depression resistant to quetiapine, and may contribute to alleviate the burden of this disabling condition.

Intervention(s) in this Clinical Trial

• Drug: quetiapine plus Liothyronine (T3)
  • quetiapine up to 300 mg a day plus liothyronine (T3) up to 50 micrograms a day
• Drug: quetiapine plus placebo
  • quetiapine up to 300 mg a day plus placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • quetiapine plus liothyronine (T3)
• Active Comparator: 2
  • quetiapine plus placebo

Primary Measures

• Hamilton Rating Scale for Depression scores
  • Time Frame: 8 weeks
    Safety Issue?: No

Secondary Measures

• Clinician-Administered Rating Scale for Mania
  • Time Frame: 8 weeks
    Safety Issue?: No
• Clinical Global Impression scores
  • Time Frame: 8 weeks
    Safety Issue?: No

Inclusion Criteria:

• 1. Age 18-60;
• 2. DSM-IV diagnosis of BP I or BP II as per SCID;
• 3. Currently in a major depressive episode (DSM-IV criteria) with at least moderate levels of depression (HAM-D > 20);
• 4. Patient has to be on stable dose of lithium or valproate for at least 4 weeks, and therapeutic blood level - valproate - 50 to 125 mcg/mL, lithium 0.6 to 1.2 mEq/L;
• 5. Not in use of any antidepressants for the past 4 weeks;
• 6. Antipsychotics other than quetiapine are allowed if there were no changes in doses for 4 weeks or more.

Exclusion Criteria:

• 1. Evidence of psychosis in the current episode (as per SCID);
• 2. Evidence of acute mania or hypomania (as measured by CARS-M > 7);
• 3. Abnormal (outside of lab normal range) thyroid function tests;
• 4. Current thyroid hormone treatment;
• 5. Any medical condition considered a contraindication for treatment with T3 (i.e.
• history of myocardial infarction, cardiac arrhythmia, severe cardiac insufficiency, previous or current thyroid adenoma, hyperthyroidism);
• 6. EKG showing rhythm other than sinus or repolarization phase abnormalities.
• 7. Current alcohol or substance abuse or dependence in past month as per SCID;
• 8. Score of 3 or more on the suicide item of the HAM-D;
• 9. Females who are pregnant, breastfeeding, or of childbearing age and not using adequate birth control.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Shore Long Island Jewish Health System

Overall Clinical Trial Officials and Contacts

Anil K Malhotra, MD Principal Investigator The Zucker Hillside Hospital, North Shore - LIJHS, The Feinstein Institute for Medical Research  

Overall Contact: Anu Tyagi (718) 470- 8146 atyagi@nshs.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00790738

Study ID Number: 08-001

ClinicalTrials.gov Identifier: NCT00790738

Health Authority: United States: Institutional Review Board