Brain Energy Metabolism in Individuals With Major Depressive Disorder Receiving Escitalopram

• ClinicalTrials.gov Identifier: NCT00183677
• Recruitment Status: Completed
• First Posted: September 16, 2005
• Results First Posted: January 4, 2017
• Last Update Posted: January 4, 2017
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): David Mischoulon, MD, Massachusetts General Hospital

Study Description

Brief Summary:

This study will evaluate changes in brain energy metabolism due to treatment with escitalopram in people with major depressive disorder.

Condition or disease	Intervention/treatment	Phase
Depression	Drug: Escitalopram	Phase 4

Detailed Description:

Major depressive disorder (MDD) is a severe form of depression. MDD can significantly interfere with an individual's thoughts, behavior, mood, and physical health. People who suffer from MDD often experience feelings of worthlessness; they may feel hopeless and may be unable to cope with problems in their life. In addition, they often experience sleep disruption, loss of appetite, and chronic pain.

Antidepressant medications are often prescribed for treating MDD; however, 30% to 40% of individuals fail to respond adequately to medication. Preliminary research has shown that lower levels of brain energy metabolism are often associated with MDD. No studies have yet shown whether there is a difference in brain energy metabolism between individuals who respond well to antidepressants versus those who do not. Escitalopram is an antidepressant medication often used to treat MDD. It causes a calming effect and reduces anxiety by increasing the amount of serotonin in the brain. This study will compare the changes in brain energy metabolism due to treatment with escitalopram in individuals with MDD. In turn, these findings may aid in understanding the relationship between brain energy metabolism and depression, and may guide future antidepressant trials.

This 12-week study will enroll individuals diagnosed with MDD, as well as healthy individuals. During Weeks 1 through 4, participants with MDD will receive 10 mg of escitalopram on a daily basis. If a participant does not respond well to the medication, as determined by the study clinician, the dose may be increased to 20 mg per day for Weeks 5 through 8. If a participant continues to not respond to the medication after 8 weeks, the dose may be increased to 30 mg per day for Weeks 9 through 12. Study visits will occur every other week throughout the 12 weeks. Laboratory tests, physical examinations, and vital sign measurements will be performed at each study visit. Outcome measurements will include depression levels as assessed by standardized psychological tests and questionnaires, as well as brain energy metabolite levels as assessed by magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) scans. The MRS and MRI scans will occur at baseline, Week 2, and Week 12; the entire scanning procedure will last 70-80 minutes. Following the end of the study, all participants will be offered follow-up medical care for 3 months. Participants who responded well to escitalopram will be offered continued treatment with the drug, while those who did not respond well to escitalopram will be offered treatment with another antidepressant.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Biochemical Brain Changes Correlated With the Antidepressant Effect of Escitalopram: A Magnetic Resonance Spectroscopic Imaging Study
• Study Start Date: July 2003
• Actual Primary Completion Date: June 2009
• Actual Study Completion Date: June 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Escitalopram; Participants will receive open treatment with escitalopram.	Drug: Escitalopram; Escitalopram 10 to 30 mg per day for 12 weeks; Other Name: Lexapro

Outcome Measures

Primary Outcome Measures :

1. Responder and Remission Status (%), Based on the Depression Rating Scale Score [ Time Frame: Measured at Week 12 ]
   The Hamilton Depression Rating Scale, 17 items (HAMD-17, range 0-52) was used to measure changes in depression severity from baseline to endpoint. Clinical Responder status was defined as > 50% improvement (i.e., reduction) in HAMD-17 score from baseline to endpoint. Clinical Remission status was defined as HAMD-17 score < 8 at endpoint (week 12 visit).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

For depressed subjects:

• Meets DSM-IV diagnostic criteria for major depressive disorder
• Score of greater than 16 on the Hamilton Depression Rating scale (17 items) at study entry
• Agrees to use an effective form of contraception throughout the study

For healthy volunteers:

• Not currently taking any medications
• No lifetime history of major neurological, medical, psychiatric disorder, or head injury
• Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:

• Current suicidal ideation that may make study participation unsafe
• Current serious or unstable medical illness (e.g., cardiovascular, kidney, liver, respiratory, endocrine, neurologic, or blood-related disease)
• History of seizure disorder
• History of or current DSM-IV diagnosis of any of the following psychiatric illnesses within 12 months of study entry: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, mood congruent or mood incongruent psychotic features, substance dependence disorders (including alcohol)
• History of or current diagnosis of dementia, or a score of less than 26 on the Mini Mental Status Examination at screening
• History of multiple adverse drug reactions or allergic reaction to the study drugs
• Currently taking psychotropic drugs or antidepressant medications
• Clinical or laboratory evidence of hypothyroidism
• Failure to respond during current major depressive episode to at least one adequate antidepressant trial, defined as 6 weeks or more of treatment with 40 mg of citalopram per day (or its antidepressant equivalent)
• History of electroconvulsive therapy (ECT) within the 6 months prior to study entry
• Pregnant
• Subjects with a CGI score a 6 ("severely depressed") or 7 ("among the most extremely depressed patients")
• A BMI of 39 or greater, for comfort in scanner

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Dan V. Iosifescu, MD; Massachusetts General Hospital

More Information

• Responsible Party: David Mischoulon, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00183677
• Other Study ID Numbers: K23MH067111 ( U.S. NIH Grant/Contract )
• First Posted: September 16, 2005
• Results First Posted: January 4, 2017
• Last Update Posted: January 4, 2017
• Last Verified: November 2016

Keywords provided by David Mischoulon, MD, Massachusetts General Hospital:

Brain Bioenergetic Metabolism; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Treatment Response

Additional relevant MeSH terms:

Depressive Disorder; Mood Disorders; Mental Disorders; Citalopram; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs