Brain Energy Metabolism in Individuals With Major Depressive Disorder Receiving Escitalopram
Brain Energy Metabolism in Individuals With Major Depressive Disorder Receiving Escitalopram
This study will evaluate changes in brain energy metabolism due to treatment with
 escitalopram in people with major depressive disorder.
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.
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