Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression

Bipolar Disorder Clinical Trial

Official title:

Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01528839
• Other study ID #: 1908Si267
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 6, 2012
• Last updated: February 7, 2012
• Start date: March 2004
• Est. completion date: August 2008

Study information

• Verified date: February 2012
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is growing evidence that thyroid axis dysfunction may contribute to the pathophysiology of bipolar illness. Open-label studies have consistently demonstrated that the behavioral expression of bipolar disorder can be modified by a change in thyroid status, and in many instances the course of illness is improved through the use of adjunct thyroid hormone treatment. Recent evidence emerged from acute intervention studies that add-on treatment with supraphysiological doses of levothyroxine is an effective augmenting agent in patients with a major depressive episode. The primary goal of this international multicenter trial (5 sites) is to determine in a 13-week, randomized, placebo-controlled design (1 week single-blind placebo run-in, 6 week double-blind, 6 week open-label) the efficacy and safety of add-on treatment with levothyroxine (300 mcg/d) in combination with mood stabilizer/antidepressant therapy in the treatment of patients with bipolar depression. The main hypotheses is: treatment with levothyroxine will result in a significantly greater mean reduction of HRSD total score and in a higher number of responders and remitters compared to placebo treatment. This proposal will build on our pilot data and provide evidence for the use of levothyroxine as an effective augmentation strategy in the treatment of bipolar depression.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: August 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis of bipolar I or II disorder, currently depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)

• Hamilton Rating Scale for Depression (HAM-D) 17-item score =14, a HAM-D item 1 (depressed mood) score =2 at the screening and randomization visits

• Young Mania Rating Scale (YMRS) score =12 at the screening and randomization visits.

• Pretreatment with a mood stabilizer and/or an antidepressant at standard doses (Bauer et al. 2007a) for at least six weeks since the last dose adjustment, and for at least two weeks before enrollment

• Serum levels of mood stabilizer were required to be within therapeutic ranges

• TSH levels in normal range (serum TSH 0.3 - 4.7 mU/l)

Exclusion Criteria:

• Any axis I disorder other than bipolar disorder

• Recent ultra-rapid cycling course (12 or more episodes in previous year), - - a diagnosis of substance dependence (DSM-IV) or substance use (except for nicotine) within 12 months before the screening visit

• Clinically significant medical illness, especially severe cardiovascular diseases

• Organic brain disorder

• Current serious suicidal or homicidal risk by clinical judgment of the investigator

• History of previous or current thyroid disease

• Thyroid hormone treatment

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression

Intervention

Drug:
• L-Thyroxine
L-Thyroxine as addon to ongoing stable antidepressant and /or mood stabilizing therapy: week 1: 100 mcg; week 2: 200 mcg: week 3 to week 6: 300 mcg
• Placebo

Locations

Country	Name	City	State
Germany	Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany	Berlin
Germany	Department of Psychiatry, LWL University Hospital, Ruhr University Bochum, Bochum, Germany	Bochum
Germany	Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany	Dresden
Germany	Department of Psychiatry and Psychotherapy, University of Göttingen, Germany	Göttingen
United States	University of California in Los Angeles	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Stanley Medical Research Institute

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items)		baseline and six weeks
Secondary	Mean change and single items change in the Thyroid Symtom List (TSL)		baseline and six weeks
Secondary	Remission/Response	Rate of Resonders (>50% decline in HRDS) and Remitters (HRDS- score < 9)after l-Thyroxine addon treatment	six weeks