Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones

Major Depressive Disorder Clinical Trial

Official title:

Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00562367
• Other study ID #: 2001-P-000836
• Status: Completed
• Phase: N/A
• First received: November 20, 2007
• Last updated: November 21, 2007
• Start date: October 2001
• Est. completion date: September 2004

Study information

• Verified date: November 2007
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

We propose to investigate structural and biochemical brain abnormalities in depressed subjects, and the relationship between the presence of such abnormalities and treatment outcome. We will recruit N=20 subjects with major depression disorder and N=20 matched normal controls. The depressed subjects would have previously not responded to an adequate trial with a selective serotonin reuptake inhibitor (SSRI). These depressed subjects will be treated for 4 weeks with the same SSRI antidepressant and with adjuvant triiodothyronine (T3). Structural magnetic resonance images (MRI) and then Phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) data will be obtained two times for each patient (at the beginning and at the end of the study) and one time for the normal controls. We will measure for each depressed subject the number of white matter hyperintensities (WMH); we will also measure the degree of change from baseline in several compounds characteristic for the cellular high-energy phosphate metabolism: the phosphocreatine/inorganic phosphate ratio and the beta-nucleoside triphosphate. We will compare the severity of WMH and the high-energy phosphate metabolism in two groups of depressed subjects (those responding and those not responding to thyroid hormone augmentation) and the normal controls.

We hypothesize that:

1. All depressed subjects, when compared with normal controls, will present lower baseline levels of compounds characteristic for the high-energy phosphate metabolism.

2. Depressed subjects responding to T3 augmentation, when compared with subjects not responding to T3 augmentation, will present a larger increase of the high-energy phosphate metabolism.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• DSM-IV diagnostic criteria for MDD (diagnosed with the use of SCID)

• Written informed consent

• Men or women aged 18-65

• A baseline Hamilton-D17 score of > 16.

Exclusion Criteria:

• Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment.

• Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy)

• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease

• History of seizure disorder,

• History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, patients with substance dependence disorders, including alcohol, active within the last 12 months.

• History or current diagnosis of dementia, or a score of < 26 on the Mini Mental Status Examination (Folstein, 1975) at the screening visit.

• History of multiple adverse drug reactions or allergy to the study drugs.

• Patients with mood congruent or mood incongruent psychotic features.

• Patients having shown minimal or no response to a standard course of antidepressant treatment with an SSRI. A standard course will be defined as the following medications taken for > 4 weeks: fluoxetine > 20 mg/day, sertraline > 50 mg/day, paroxetine > 20 mg/day, fluvoxamine > 50 mg/day, citalopram > 20 mg/day, venlafaxine > 150 mg/day.

• Clinical or laboratory evidence of hypothyroidism.

• Patients who have had electroconvulsive therapy (ECT) within the 6 months preceding baseline.

• History of intolerance to Cytomel

• History of cardiac pathology or diabetes

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Cytomel (liothyronine)
Cytomel (liothyronine) 25-50 mcg/day for 4 weeks

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Alliance for Research on Schizophrenia and Depression

Country where clinical trial is conducted

United States, 

References & Publications (1)

Iosifescu DV, Nierenberg AA, Mischoulon D, Perlis RH, Papakostas GI, Ryan JL, Alpert JE, Fava M. An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder. J Clin Psychiatry. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in depression (as measured by Ham-D-17) over the 4 weeks study		4 weeks
Secondary	change in bioenergetic metabolism (e.g., NTP and PCr) as measured by phosphorus magnetic resonance spectroscopy (P31-MRS)		4 weeks