Time to Remission of Depressive Symptoms With Combined SSRI and Ramelteon

Hypothesis I: Patients in the SSRI + ramelteon treatment group will achieve remission (defined as an IDS-C30 score of 11 or less) more quickly than those in the SSRI + placebo group.

The primary objective of the study is to assess the time to remission in depression with initial insomnia using the SSRI antidepressant escitalopram combined with ramelteon or placebo. Patients will be assessed at each visit for depressive symptoms and insomnia, using the 30-item Inventory of Depressive Symptoms, Clinician-Rated version (IDS-C30; Rush et al 1986; Rush et al., 1996) as the primary outcome measure. The IDS self-report version will be used to assess self-reported changes in symptom severity. The 17 item Hamilton Rating Scale for Depression, (HRSD17; Hamilton, 1960) will also be administered, as it is the most commonly utilized depression symptom severity measure at this time.

Eligibility Criteria:
Inclusion Criteria:

* Ability and willingness to provide written informed consent.
* Primary diagnosis of MDD with initial insomnia.
* Age 18-70.
* Screening HRSD17 score greater than or equal to 16 or CGI-S score of at least 4.
* Subjective report of difficulties with initial insomnia with a score of 2 or greater on the IDS-C30 item addressing this symptom (#1). Middle and late insomnia may also be present so long as initial insomnia is present.

Exclusion Criteria:

* Presence of significant comorbid medical condition based on laboratory test, physician information, or evidence at examination; this includes severe sleep apnea, seizure disorder, or chronic obstructive pulmonary disease (COPD).
* Patient report or evidence (based on physical examination or laboratory tests) of significant medical abnormalities; this includes severe sleep apnea, seizure disorder, or COPD.
* Presence of other psychological disorders, including depression due to other comorbid conditions, currently suicidal or high suicide risk, current or past psychotic disorders of any type, bipolar disorder (I, II, or NOS), schizophrenia, or schizoaffective disorder, anorexia, bulimia, obsessive compulsive disorder, alcohol or substance abuse within the last 6 months, or patients with comorbid psychiatric conditions that are relative or absolute contraindications to the use of escitalopram or ramelteon.
* Concomitant (i.e. within 2 weeks; 4 weeks for fluoxetine or MAOIs) pharmacological or psychotherapeutic treatment including but not limited to anxiolytics, neuroleptics, mood stabilizers, sleep aids including over the counter melatonin, and/or other agents without proven antidepressant efficacy, cognitive behavioral therapy; current use of other medications that would be contraindicated with ramelteon or escitalopram,, as determined by the study doctor.
* Failure to respond to 2 adequate courses of SSRI class antidepressant in the current episode (as measured by the Antidepressant Treatment History Form).
* Hospitalization for mental illness within the past year.
* For women, currently pregnant, planning to become pregnant in the next year, or breastfeeding.
* Patient does not speak English. (Patient needs to be fluent in written and oral English because not all assessments are available and/or validated in languages other than English).