Clinical trial NCT01528839: Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression
Official title: Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Bipolar Disorder
Keywords: Bipolar disorder
Bipolar depression
Thyroid abnormality
mood stabilizer
antidepressants
currently depressed
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2012-02-08
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items)
timeFrame: baseline and six weeks
Secondary outcomes:
measure: Mean change and single items change in the Thyroid Symtom List (TSL)
timeFrame: baseline and six weeks
measure: Remission/Response
timeFrame: six weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California in Los Angeles
state: California
city: Berlin
country: Germany
facility: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
city: Bochum
country: Germany
facility: Department of Psychiatry, LWL University Hospital, Ruhr University Bochum, Bochum, Germany
city: Dresden
country: Germany
facility: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
city: Göttingen
country: Germany
facility: Department of Psychiatry and Psychotherapy, University of Göttingen, Germany
Study officials:
References:
citation: 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.
citation: 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.