Depression
Conditions
Keywords
Brain Bioenergetic Metabolism, Magnetic Resonance Spectroscopy, Major Depressive Disorder, Treatment Response
Brief summary
This study will evaluate changes in brain energy metabolism due to treatment with escitalopram in people with major depressive disorder.
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.
Interventions
DRUGEscitalopram
Escitalopram 10 to 30 mg per day for 12 weeks
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder and Remission Status (%), Based on the Depression Rating Scale Score | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Escitalopram Participants will receive treatment with escitalopram. | 97 |
| Total | 97 |
Baseline characteristics
| Characteristic | Open Label Escitalopram |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 97 Participants |
| Age, Continuous | 41.54 years STANDARD_DEVIATION 13.42 |
| Gender Female | 42 Participants |
| Gender Male | 55 Participants |
| Region of Enrollment United States | 97 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 97 |
| serious Total, serious adverse events | 0 / 97 |
Outcome results
Primary
Responder and Remission Status (%), Based on the Depression Rating Scale Score
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).
Time frame: Measured at Week 12
Population: 97 patients with MDD (42 Female) enrolled in the 12 week study, 53 patients (27 Female) completed. Only completers were included in the primary outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label Escitalopram | Responder and Remission Status (%), Based on the Depression Rating Scale Score | Clinical Responders | 36 participants |
| Open Label Escitalopram | Responder and Remission Status (%), Based on the Depression Rating Scale Score | Clinical Remitters | 32 participants |