Insomnia, Major Depressive Disorder
Conditions
Keywords
MDD, Major Depressive Disorder, Depression, Initial Insomnia, sleep, difficulty sleeping, down, sad, Major Depressive Disorder(MDD) and initial insomnia
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.
Interventions
DRUGEscitalopram
Escitalopram 10 or 20mg qd based on symptoms at patient visit
DRUGRamelteon
Ramelteon 8 mg qd
OTHERPlacebo
Matching placebo qd
Sponsors
Takeda Pharmaceuticals North America, Inc.
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Sleep Latency | 12 weeks | Number of minutes until fell asleep |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram + Ramelteon active augmentation | 14 |
| Escitalopram + Placebo Placebo augmentation | 15 |
| Total | 29 |
Baseline characteristics
| Characteristic | Total | Escitalopram + Ramelteon | Escitalopram + Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 14 Participants | 15 Participants |
| Age, Continuous | 42.3 years STANDARD_DEVIATION 11.6 | 42.6 years STANDARD_DEVIATION 12.4 | 42.0 years STANDARD_DEVIATION 11.4 |
| Region of Enrollment United States | 29 participants | 14 participants | 15 participants |
| Sex: Female, Male Female | 20 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 14 | 15 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 |
Outcome results
Primary
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
Time frame: 12 Weeks
Population: Participants who were randomized to treatment and completed Week 12 were included in analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram + Ramelteon | Percentage of Remitters on IDS-C30 at Week 12 | 20 percentage of participants |
| Escitalopram + Placebo | Percentage of Remitters on IDS-C30 at Week 12 | 36 percentage of participants |
p-value: 0.05Mixed Models Analysis
Secondary
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.
Time frame: 12 Weeks
Population: Please note that the study was terminated early and may be underpowered to perform these analyses; results should be interpreted with caution.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + Ramelteon | Hamilton Rating Scale for Depression 17-item | 8.33 score on a scale | Standard Deviation 6.26 |
| Escitalopram + Placebo | Hamilton Rating Scale for Depression 17-item | 10.08 score on a scale | Standard Deviation 6.36 |
Secondary
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.
Time frame: 12 Weeks
Population: Please note that the study was terminated early and may be underpowered to perform these analyses; results should be interpreted with caution.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + Ramelteon | Patient Perception of Benefits of Care (PPBC) | 20.33 score on a scale | Standard Deviation 8.38 |
| Escitalopram + Placebo | Patient Perception of Benefits of Care (PPBC) | 20.08 score on a scale | Standard Deviation 12.5 |
Secondary
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.
Time frame: 12 Weeks
Population: Please note that the study was terminated early and may be underpowered to perform these analyses; results should be interpreted with caution.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + Ramelteon | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | 69.84 score on a scale | Standard Deviation 14.44 |
| Escitalopram + Placebo | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | 70.24 score on a scale | Standard Deviation 12.27 |
Secondary
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.
Time frame: 12 Weeks
Population: Please note that the study was terminated early and may be underpowered to perform these analyses; results should be interpreted with caution.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | Physical Functioning | 80.50 score on a scale | Standard Deviation 28.43 |
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | Social Functioning | 69.44 score on a scale | Standard Deviation 37.56 |
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | Physical Role Functioning | 75.00 score on a scale | Standard Deviation 28.93 |
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | Emotional Role Functioning | 67.59 score on a scale | Standard Deviation 24.45 |
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | Mental Health | 68.00 score on a scale | Standard Deviation 25.3 |
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | Vitality | 49.38 score on a scale | Standard Deviation 27.55 |
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | Bodily Pain | 75.31 score on a scale | Standard Deviation 25.93 |
| Escitalopram + Ramelteon | Short-Form Health Survey - Version 2 (SF-36) | General Health | 74.90 score on a scale | Standard Deviation 21.12 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | General Health | 79.25 score on a scale | Standard Deviation 20.23 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | Physical Functioning | 88.33 score on a scale | Standard Deviation 16.42 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | Mental Health | 70.42 score on a scale | Standard Deviation 21.16 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | Social Functioning | 68.75 score on a scale | Standard Deviation 27.95 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | Bodily Pain | 87.96 score on a scale | Standard Deviation 19.22 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | Physical Role Functioning | 86.11 score on a scale | Standard Deviation 17.89 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | Vitality | 54.69 score on a scale | Standard Deviation 20.49 |
| Escitalopram + Placebo | Short-Form Health Survey - Version 2 (SF-36) | Emotional Role Functioning | 75.00 score on a scale | Standard Deviation 20.1 |
Secondary
Sleep Latency
Number of minutes until fell asleep
Time frame: 12 weeks
Population: Number of Participants with analyzable data for this outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + Ramelteon | Sleep Latency | 30.4 minutes | Standard Deviation 29.1 |
| Escitalopram + Placebo | Sleep Latency | 15.8 minutes | Standard Deviation 16.2 |
Secondary
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.
Time frame: 12 Weeks
Population: Please note that the study was terminated early and may be underpowered to perform these analyses; results should be interpreted with caution.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + Ramelteon | Social Adjustment Scale - Self-Report (SAS-SR) | 2.09 mean score on a scale | Standard Deviation 0.39 |
| Escitalopram + Placebo | Social Adjustment Scale - Self-Report (SAS-SR) | 2.03 mean score on a scale | Standard Deviation 0.46 |
Secondary
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.
Time frame: 12 Weeks
Population: Please note that the study was terminated early and may be underpowered to perform these analyses; results should be interpreted with caution.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + Ramelteon | Work and Social Adjustment Scale (WSAS) | 15.56 score on a scale | Standard Deviation 11.42 |
| Escitalopram + Placebo | Work and Social Adjustment Scale (WSAS) | 13.91 score on a scale | Standard Deviation 12.89 |
Secondary
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.
Time frame: 12 Weeks
Population: Please note that the study was terminated early and may be underpowered to perform these analyses; results should be interpreted with caution.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + Ramelteon | Work Productivity and Activity Impairment Questionnaire (WPAI) | 40.00 percentage of time activity was impaired | Standard Deviation 35.36 |
| Escitalopram + Placebo | Work Productivity and Activity Impairment Questionnaire (WPAI) | 32.50 percentage of time activity was impaired | Standard Deviation 27.34 |