Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression

This study has been completed.
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Thomas Stamm, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01528839
First received: February 6, 2012
Last updated: February 7, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Drug: L-Thyroxine
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items) [ Time Frame: baseline and six weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean change and single items change in the Thyroid Symtom List (TSL) [ Time Frame: baseline and six weeks ] [ Designated as safety issue: Yes ]
  • Remission/Response [ Time Frame: six weeks ] [ Designated as safety issue: No ]
    Rate of Resonders (>50% decline in HRDS) and Remitters (HRDS- score < 9)after l-Thyroxine addon treatment


Enrollment: 74
Study Start Date: March 2004
Study Completion Date: August 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Pill Drug: Placebo
Experimental: L-Thyroxine as addon 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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01528839

Locations
United States, California
University of California in Los Angeles
Los Angeles, California, United States
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, Germany
Sponsors and Collaborators
Charite University, Berlin, Germany
Stanley Medical Research Institute
  More Information

No publications provided by Charite University, Berlin, Germany

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas Stamm, Associate Director Mood Disorders Research Group Department of Psychiatry and Psychotherapy CCM, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01528839     History of Changes
Other Study ID Numbers: 1908Si267
Study First Received: February 6, 2012
Last Updated: February 7, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
Bipolar disorder
Bipolar depression
Thyroid abnormality
mood stabilizer
antidepressants
currently depressed

Additional relevant MeSH terms:
Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Affective Disorders, Psychotic

ClinicalTrials.gov processed this record on October 19, 2014