Bipolar Disorder, Depression
Conditions
Keywords
bipolar disorder, depression, treatment, randomized controlled trial
Brief summary
This study evaluates the efficacy of the thyroid hormone T3 for depression in patients with bipolar disorder. In this study patients will be randomized to receive T3 or placebo.
Detailed description
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.
Interventions
DRUGLiothyronine (T3)
liothyronine (T3) up to 50 micrograms a day
DRUGplacebo
placebo
Sponsors
National Alliance for Research on Schizophrenia and Depression
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Rating Scale for Depression Scores | 8 weeks | The Hamilton Rating Scale for Depression (HRSD) is a checklist of items ranked from 0-4 or 0-2, that was designed to measure the severity of depressive symptoms. The scale ranges from 0 to 50, and the following thresholds are used: very severe \>23, severe 19-22, moderate 14-18, mild 8-13 and normal ≤7. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Administered Rating Scale for Mania | 8 weeks | The Clinician-Administered Rating Scale for Mania (CARS-M) contains 15 items rated from 0-5 or 0-6 on a Likert scale. It was developed to assess severity of manic symtoms. The scale ranges from 0 to 50, and the following thresholds are used: severe ≥26, moderate 16-25, mild 8-15 and normal ≤7. |
| Clinical Global Impression Scores | 8 weeks | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. At the time of rating patients are rated as: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liothyronine (T3) liothyronine (T3)
Liothyronine (T3): liothyronine (T3) up to 50 micrograms a day | 5 |
| Placebo placebo
placebo: placebo | 6 |
| Total | 11 |
Baseline characteristics
| Characteristic | Total | Liothyronine (T3) | Placebo |
|---|---|---|---|
| Age, Continuous | 45.2 years STANDARD_DEVIATION 7.4 | 43.8 years STANDARD_DEVIATION 9.5 | 46.4 years STANDARD_DEVIATION 5.9 |
| Region of Enrollment United States | 11 participants | 5 participants | 6 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 5 | 4 / 6 |
| serious Total, serious adverse events | 0 / 5 | 1 / 6 |
Outcome results
Primary
Hamilton Rating Scale for Depression Scores
The Hamilton Rating Scale for Depression (HRSD) is a checklist of items ranked from 0-4 or 0-2, that was designed to measure the severity of depressive symptoms. The scale ranges from 0 to 50, and the following thresholds are used: very severe \>23, severe 19-22, moderate 14-18, mild 8-13 and normal ≤7.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liothyronine (T3) | Hamilton Rating Scale for Depression Scores | 3.50 units on a scale | Standard Deviation 3.54 |
| Placebo | Hamilton Rating Scale for Depression Scores | 7.25 units on a scale | Standard Deviation 5.44 |
Secondary
Clinical Global Impression Scores
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. At the time of rating patients are rated as: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liothyronine (T3) | Clinical Global Impression Scores | 4 units on a scale | Standard Deviation 0 |
| Placebo | Clinical Global Impression Scores | 3 units on a scale | Standard Deviation 0 |
Secondary
Clinician-Administered Rating Scale for Mania
The Clinician-Administered Rating Scale for Mania (CARS-M) contains 15 items rated from 0-5 or 0-6 on a Likert scale. It was developed to assess severity of manic symtoms. The scale ranges from 0 to 50, and the following thresholds are used: severe ≥26, moderate 16-25, mild 8-15 and normal ≤7.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liothyronine (T3) | Clinician-Administered Rating Scale for Mania | 0.5 units on a scale | Standard Deviation 0.71 |
| Placebo | Clinician-Administered Rating Scale for Mania | 2 units on a scale | Standard Deviation 1.82 |