Time to Remission of Depressive Symptoms With Combined SSRI and Ramelteon

Phase 3

Terminated

Conditions: Major Depressive Disorder
Insomnia

Interventions: Drug: Escitalopram
Other: Placebo
Drug: Ramelteon

Registration Number: NCT00642694

Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 29

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Escitalopram tablets (starting dose of 10 mg with a maximum dose of 20 mg daily) + Matching Placebo (One capsule at night)
1	Escitalopram	Escitalopram tablets (starting dose of 10 mg with a maximum dose of 20 mg daily) + Ramelteon (One 8 mg capsule at night)
1	Ramelteon	Escitalopram tablets (starting dose of 10 mg with a maximum dose of 20 mg daily) + Ramelteon (One 8 mg capsule at night)
2	Escitalopram	Escitalopram tablets (starting dose of 10 mg with a maximum dose of 20 mg daily) + Matching Placebo (One capsule at night)

Primary Outcome Measures

Name	Time	Method
Percentage of Remitters on IDS-C30 at Week 12	12 Weeks	Remission as defined by a score of \<12 on the Inventory of Depressive Symptomatology, Clinician-Rated version (IDS-C30) at Week 12; minimum possible score = 0, maximum possible score = 84; higher scores indicate worse symptom severity

Secondary Outcome Measures

Name	Time	Method
Sleep Latency	12 weeks	Number of minutes until fell asleep
Short-Form Health Survey - Version 2 (SF-36)	12 Weeks	The Short-Form Health Survey - version 2 (SF-36) is a self-report inventory measuring different domains of health-related quality of life: Physical Functioning, Physical Role Functioning, Bodily Pain, General Health, Vitality, Social Functioning, Emotional Role Functioning, and Mental Health. Scores range from 0 to 100, with higher scores indicating better perceived health and functioning.
Social Adjustment Scale - Self-Report (SAS-SR)	12 Weeks	The Social Adjustment Scale - Self-Report (SAS-SR) is a 54-item self-report measure of instrumental and expressive role performance. Each item is rated on a 5-point scale, and a mean item score (ranging from 1-5) is obtained, with higher scores indicating greater impairment.
Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)	12 Weeks	The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) measures satisfaction and enjoyment in various domains of functioning: physical health, feelings, work, household duties, school/course work, leisure time activities, social relations, and general activities. The raw score is converted into a percent of the maximum possible score and ranges from 0 to 100. Higher scores indicate greater enjoyment and satisfaction.
Work and Social Adjustment Scale (WSAS)	12 Weeks	The Work and Social Adjustment Scale (WSAS) is 5-item self-report measure designed to identify functional impairment that is attributed to an identified problem or condition. and has been used in studies of depression and anxiety. Scores range between 0-40, with higher scores indicating worse functioning.
Patient Perception of Benefits of Care (PPBC)	12 Weeks	The Patient Perception of Benefits of Care (PPBC) assesses how much patients believe their quality of life will improve in response to medical care or treatment. Scores range between 10-50, with lower scores indicating greater belief that treatment will improve quality of life.
Work Productivity and Activity Impairment Questionnaire (WPAI)	12 Weeks	The Work Productivity and Activity Impairment Questionnaire (WPAI) was used to report impairment while working or performing usual daily activities as a result of health problems. The activity impairment item (#6 of WPAI) is rated on a scale of 0-10, with higher scores indicating greater impairment. Scores are multiplied by 10 to obtain percent impairment.
Hamilton Rating Scale for Depression 17-item	12 Weeks	The Hamilton Rating Scale for Depression is a clinician-administered rating scale that assesses severity of depressive symptoms and is one of the most widely used and validated symptom severity measures for depression. Each of the 17 items is rated by the clinician on either a 3- or a 5 point scale. Total scores range from 0-52, with higher scores indicating greater depressive symptoms.