Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression

NCT01528839 | Completed Phase 2 DMC

• 1 other identifier: 1908Si267
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 5

Brief 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.

Conditions

Bipolar Disorder

Keywords

Bipolar disorder; Bipolar depression; Thyroid abnormality; mood stabilizer; antidepressants; currently depressed

Outcome Measures

Primary Outcomes (1)

• Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items)

  baseline and six weeks

Secondary Outcomes (2)

• Mean change and single items change in the Thyroid Symtom List (TSL)

  baseline and six weeks

• Remission/Response

  six weeks

Study Arms (2)

Pill

PLACEBO COMPARATOR

Drug: Placebo

L-Thyroxine as addon

EXPERIMENTAL

Drug: L-Thyroxine

Interventions

L-Thyroxine DRUG

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

L-Thyroxine as addon

Placebo DRUG

Pill

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Stanley Medical Research Institute: collaborator

Study Sites (5)

University of California in Los Angeles

Los Angeles, California, United States

Location

Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany

Berlin, Germany

Location

Department of Psychiatry, LWL University Hospital, Ruhr University Bochum, Bochum, Germany

Bochum, Germany

Location

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Dresden, Germany

Location

Department of Psychiatry and Psychotherapy, University of Göttingen, Germany

Göttingen, Germany

Location

Related Publications (2)

• Pilhatsch M, J Stamm T, Stahl P, Lewitzka U, Berghofer A, Sauer C, Gitlin M, Frye MA, Whybrow PC, Bauer M. Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms. Int J Bipolar Disord. 2019 Oct 4;7(1):21. doi: 10.1186/s40345-019-0155-y.

  PMID: 31583561 DERIVED

• Stamm TJ, Lewitzka U, Sauer C, Pilhatsch M, Smolka MN, Koeberle U, Adli M, Ricken R, Scherk H, Frye MA, Juckel G, Assion HJ, Gitlin M, Whybrow PC, Bauer M. Supraphysiologic doses of levothyroxine as adjunctive therapy in bipolar depression: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014 Feb;75(2):162-8. doi: 10.4088/JCP.12m08305.

  PMID: 24345793 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director Mood Disorders Research Group Department of Psychiatry and Psychotherapy CCM

Study Record Dates

• First Submitted: February 6, 2012
• First Posted: February 8, 2012
• Study Start: March 1, 2004
• Primary Completion: May 1, 2008
• Study Completion: August 1, 2008
• Last Updated: February 8, 2012

Record last verified: 2012-02

Locations

DE (4); US (1)