Time to Remission of Depressive Symptoms With Combined SSRI and Ramelteon (TAKEDA)

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.

Study Overview

• Status: Terminated
• Conditions: Insomnia; Major Depressive Disorder
• Intervention / Treatment: Drug: Escitalopram; Drug: Ramelteon; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 752390-9119
      • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Escitalopram tablets (starting dose of 10 mg with a maximum dose of 20 mg daily) + Ramelteon (One 8 mg capsule at night)	Drug: Escitalopram; Escitalopram 10 or 20mg qd based on symptoms at patient visit; Other Names: Lexapro (escitalopram); Drug: Ramelteon; Ramelteon 8 mg qd; Other Names: Rozerem (Ramelteon)
Placebo Comparator: 2; Escitalopram tablets (starting dose of 10 mg with a maximum dose of 20 mg daily) + Matching Placebo (One capsule at night)	Drug: Escitalopram; Escitalopram 10 or 20mg qd based on symptoms at patient visit; Other Names: Lexapro (escitalopram); Other: Placebo; Matching placebo qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Remitters on IDS-C30 at Week 12	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	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Latency	Number of minutes until fell asleep	12 weeks
Short-Form Health Survey - Version 2 (SF-36)	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.	12 Weeks
Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)	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.	12 Weeks
Social Adjustment Scale - Self-Report (SAS-SR)	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.	12 Weeks
Work and Social Adjustment Scale (WSAS)	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.	12 Weeks
Work Productivity and Activity Impairment Questionnaire (WPAI)	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.	12 Weeks
Patient Perception of Benefits of Care (PPBC)	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.	12 Weeks
Hamilton Rating Scale for Depression 17-item	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.	12 Weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Takeda Pharmaceuticals North America, Inc.

Publications and helpful links

Helpful Links

• Mood Disorders Research Program and Clinic

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: March 19, 2008
• First Submitted That Met QC Criteria: March 24, 2008
• First Posted (Estimate): March 25, 2008

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: July 3, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Depression; sleep; MDD; Major Depressive Disorder; sad; difficulty sleeping; Initial Insomnia; down; Major Depressive Disorder(MDD) and initial insomnia
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Depression; Depressive Disorder; Sleep Initiation and Maintenance Disorders; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide
• Other Study ID Numbers: 06-031R; 112006-017