Major Depressive Disorder
Conditions
Brief summary
To compare the efficacy of escitalopram fixed dose 20 mg/day in combination with fixed doses of gaboxadol (5 and 10 mg/day) versus escitalopram fixed dose 20 mg/day after 8 weeks of treatment in patients with Major Depressive Disorder
Detailed description
Subjects participating in this study will be respectively randomised (1:2:2:2) to receive either: * placebo or * escitalopram 20 mg/day or * escitalopram 20 mg/day in combination with gaboxadol 5 mg/day or * escitalopram 20 mg/day in combination with gaboxadol 10 mg/day
Interventions
Once daily before bedtime for 8 weeks
DRUGGaboxadol placebo
Once daily before bedtime for 8 weeks
Once daily before bedtime for 8 weeks
DRUGGaboxadol 5 mg
Once daily before bedtime for 8 weeks
DRUGGaboxadol 10 mg
Once daily before bedtime for 8 weeks
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Clinical Diagnosis of MDD according to DSM-IV-TR criteria: * With reported duration of the current major depressive episode of at least 3 months * With MADRS total score of at least 30
Exclusion criteria
The patient has 1 or more of the following: * Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR * Current or past history of: manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR * Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR * Presence or history of a clinically significant neurological disorder (including epilepsy) * Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc) * Any Axis II disorder that might compromise the study * Previous use of hallucinogenic drug The patient has a significant risk of suicide according to the investigator's opinion, or has a score \>=5 on item 10 (suicidal thoughts) of the MADRS, or has made a suicide attempt in the previous 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery and Åsberg Depression Rating Scale (MADRS) | Baseline to 8 weeks | The MADRS is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at 2-point intervals. The total score of the 10 items ranges from 0 to 60. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Anxiety and Depression Scale (HADS) | Mean change from baseline to Week 8 | The HADS is a patient-rated scale designed to screen for anxiety and depressive states in medical patients. It consists of two sub-scales: the D-scale measures depression and the A-scale measures anxiety. Each sub-scale contains 7 items, and each item is rated from 0 (absent) to 3 (maximum severity). The score of each sub-scale ranges from 0 to 21, and are analysed separately. The total HADS score ranges from 0 to 42. |
| Insomnia Severity Index (ISI) | Mean change from baseline to Week 8 | The ISI is both a brief screening measure of insomnia and an outcomes measure for use in treatment research. It is a brief self-report instrument measuring the patient's perception of his or her insomnia, and it comprises 7 items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28. 0 = no symptoms and 28 = severe symptoms. |
| Sheehan Disability Scale (SDS): Family Subscale | Mean change from baseline to Week 8 | The SDS comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. |
| MADRS | From baseline to Week 8 | The MADRS is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at 2-point intervals. The total score of the 10 items ranges from 0 to 60. |
| SDS: Social Subscale | Mean change from baseline to Week 8 | The SDS comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. |
| Clinical Global Impression - Severity of Illness (CGI-S) | Mean change from baseline to Week 8 | The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). |
| Clinical Global Impression - Global Improvement (CGI-I) | at Week 8 | The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). |
| SDS: Work Subscale | Mean change from baseline to Week 8 | The SDS comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. |
Countries
Austria, Russia
Participant flow
Recruitment details
The patients were recruited from specialist inpatient and outpatient clinics.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Orally, Once Daily) | 71 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | 140 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | 139 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | 140 |
| Total | 490 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 | 6 |
| Overall Study | Lack of Efficacy | 14 | 4 | 8 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Other Reason | 0 | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal of Consent | 5 | 5 | 5 | 5 |
Baseline characteristics
| Characteristic | Total | Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | Placebo (Orally, Once Daily) | Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | Escitalopram 20 mg and Placebo (Orally, Once Daily) |
|---|---|---|---|---|---|
| Age Continuous | 42.0 years STANDARD_DEVIATION 11.7 | 41.5 years STANDARD_DEVIATION 10.5 | 42.6 years STANDARD_DEVIATION 11.6 | 42.6 years STANDARD_DEVIATION 11.8 | 41.6 years STANDARD_DEVIATION 12.6 |
| Clinical Global Impression - Severity of Illness (CGI-S) | 4.4 Scores on a scale STANDARD_DEVIATION 0.9 | 4.4 Scores on a scale STANDARD_DEVIATION 0.9 | 4.4 Scores on a scale STANDARD_DEVIATION 0.9 | 4.3 Scores on a scale STANDARD_DEVIATION 0.9 | 4.5 Scores on a scale STANDARD_DEVIATION 0.9 |
| Hospital Anxiety and Depression Scale (HADS) | 27.8 Scores on a scale STANDARD_DEVIATION 5.5 | 27.4 Scores on a scale STANDARD_DEVIATION 5.5 | 27.5 Scores on a scale STANDARD_DEVIATION 5.9 | 28.1 Scores on a scale STANDARD_DEVIATION 5.5 | 28.2 Scores on a scale STANDARD_DEVIATION 5.3 |
| Insomnia Severity Index (ISI) | 18.3 Scores on a scale STANDARD_DEVIATION 4.7 | 18.1 Scores on a scale STANDARD_DEVIATION 4.8 | 18.4 Scores on a scale STANDARD_DEVIATION 5 | 18.2 Scores on a scale STANDARD_DEVIATION 4.4 | 18.6 Scores on a scale STANDARD_DEVIATION 4.7 |
| Montgomery and Åsberg Depression Rating Scale (MADRS) | 35.1 Scores on a scale STANDARD_DEVIATION 3.9 | 34.7 Scores on a scale STANDARD_DEVIATION 3.8 | 34.7 Scores on a scale STANDARD_DEVIATION 4.2 | 35.3 Scores on a scale STANDARD_DEVIATION 3.4 | 35.4 Scores on a scale STANDARD_DEVIATION 4.3 |
| SDS: Social Subscale | 7.0 Scores on a scale STANDARD_DEVIATION 1.5 | 6.9 Scores on a scale STANDARD_DEVIATION 1.6 | 7.0 Scores on a scale STANDARD_DEVIATION 1.4 | 7.1 Scores on a scale STANDARD_DEVIATION 1.5 | 7.1 Scores on a scale STANDARD_DEVIATION 1.4 |
| SDS: Work Subscale | 7.2 Scores on a scale STANDARD_DEVIATION 1.4 | 7.0 Scores on a scale STANDARD_DEVIATION 1.4 | 7.3 Scores on a scale STANDARD_DEVIATION 1.2 | 7.3 Scores on a scale STANDARD_DEVIATION 1.5 | 7.4 Scores on a scale STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 338 Participants | 93 Participants | 53 Participants | 96 Participants | 96 Participants |
| Sex: Female, Male Male | 152 Participants | 47 Participants | 18 Participants | 43 Participants | 44 Participants |
| Sheehan Disability Scale (SDS): Family Subscale | 7.1 Scores on a scale STANDARD_DEVIATION 1.4 | 6.9 Scores on a scale STANDARD_DEVIATION 1.4 | 7.0 Scores on a scale STANDARD_DEVIATION 1.4 | 7.2 Scores on a scale STANDARD_DEVIATION 1.3 | 7.1 Scores on a scale STANDARD_DEVIATION 1.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 71 | 22 / 140 | 31 / 139 | 19 / 140 |
| serious Total, serious adverse events | 1 / 71 | 0 / 140 | 0 / 139 | 0 / 140 |
Outcome results
Primary
Montgomery and Åsberg Depression Rating Scale (MADRS)
The MADRS is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at 2-point intervals. The total score of the 10 items ranges from 0 to 60.
Time frame: Baseline to 8 weeks
Population: Mean change from baseline to Week 8: Full-analysis Set (FAS), Last Observation Carried Forward (LOCF), Analysis of Covariance (ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | Montgomery and Åsberg Depression Rating Scale (MADRS) | -13.4 Scores on a scale | Standard Error 1.1 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | Montgomery and Åsberg Depression Rating Scale (MADRS) | -19.0 Scores on a scale | Standard Error 0.9 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | Montgomery and Åsberg Depression Rating Scale (MADRS) | -18.5 Scores on a scale | Standard Error 0.9 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | Montgomery and Åsberg Depression Rating Scale (MADRS) | -19.4 Scores on a scale | Standard Error 0.9 |
p-value: 0.640595% CI: [-2.34, 1.44]ANCOVA
p-value: 0.622795% CI: [-1.41, 2.35]ANCOVA
Secondary
Clinical Global Impression - Global Improvement (CGI-I)
The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: at Week 8
Population: At Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | Clinical Global Impression - Global Improvement (CGI-I) | 2.97 Scores on a scale | Standard Error 0.12 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | Clinical Global Impression - Global Improvement (CGI-I) | 2.21 Scores on a scale | Standard Error 0.09 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | Clinical Global Impression - Global Improvement (CGI-I) | 2.35 Scores on a scale | Standard Error 0.09 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | Clinical Global Impression - Global Improvement (CGI-I) | 2.26 Scores on a scale | Standard Error 0.09 |
p-value: <0.000195% CI: [-1.02, -0.5]ANCOVA
p-value: <0.000195% CI: [-0.88, -0.36]ANCOVA
p-value: <0.000195% CI: [-0.97, -0.45]ANCOVA
Secondary
Clinical Global Impression - Severity of Illness (CGI-S)
The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients).
Time frame: Mean change from baseline to Week 8
Population: Mean change from baseline to Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | Clinical Global Impression - Severity of Illness (CGI-S) | -1.04 Scores on a scale | Standard Error 0.13 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | Clinical Global Impression - Severity of Illness (CGI-S) | -1.65 Scores on a scale | Standard Error 0.1 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | Clinical Global Impression - Severity of Illness (CGI-S) | -1.58 Scores on a scale | Standard Error 0.1 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | Clinical Global Impression - Severity of Illness (CGI-S) | -1.76 Scores on a scale | Standard Error 0.1 |
p-value: <0.000195% CI: [-0.89, -0.34]ANCOVA
p-value: 0.000195% CI: [-0.82, -0.26]ANCOVA
p-value: <0.000195% CI: [-0.99, -0.44]ANCOVA
Secondary
Hospital Anxiety and Depression Scale (HADS)
The HADS is a patient-rated scale designed to screen for anxiety and depressive states in medical patients. It consists of two sub-scales: the D-scale measures depression and the A-scale measures anxiety. Each sub-scale contains 7 items, and each item is rated from 0 (absent) to 3 (maximum severity). The score of each sub-scale ranges from 0 to 21, and are analysed separately. The total HADS score ranges from 0 to 42.
Time frame: Mean change from baseline to Week 8
Population: Mean change from baseline to Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | Hospital Anxiety and Depression Scale (HADS) | -9.7 Scores on a scale | Standard Error 1 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | Hospital Anxiety and Depression Scale (HADS) | -14.7 Scores on a scale | Standard Error 0.8 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | Hospital Anxiety and Depression Scale (HADS) | -14.1 Scores on a scale | Standard Error 0.8 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | Hospital Anxiety and Depression Scale (HADS) | -15.0 Scores on a scale | Standard Error 0.7 |
p-value: <0.000195% CI: [-7.13, -2.84]ANCOVA
p-value: <0.000195% CI: [-6.6, -2.32]ANCOVA
p-value: <0.000195% CI: [-7.41, -3.13]ANCOVA
Secondary
Insomnia Severity Index (ISI)
The ISI is both a brief screening measure of insomnia and an outcomes measure for use in treatment research. It is a brief self-report instrument measuring the patient's perception of his or her insomnia, and it comprises 7 items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28. 0 = no symptoms and 28 = severe symptoms.
Time frame: Mean change from baseline to Week 8
Population: Mean change from baseline to Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | Insomnia Severity Index (ISI) | -6.9 Scores on a scale | Standard Error 0.7 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | Insomnia Severity Index (ISI) | -10.0 Scores on a scale | Standard Error 0.5 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | Insomnia Severity Index (ISI) | -9.6 Scores on a scale | Standard Error 0.5 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | Insomnia Severity Index (ISI) | -10.6 Scores on a scale | Standard Error 0.5 |
p-value: <0.000195% CI: [-4.59, -1.58]ANCOVA
p-value: 0.000695% CI: [-4.15, -1.14]ANCOVA
p-value: <0.000195% CI: [-5.13, -2.1]ANCOVA
Secondary
MADRS
The MADRS is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at 2-point intervals. The total score of the 10 items ranges from 0 to 60.
Time frame: From baseline to Week 8
Population: Mean change from baseline to Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | MADRS | -13.4 Scores on a scale | Standard Error 1.1 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | MADRS | -19.0 Scores on a scale | Standard Error 0.9 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | MADRS | -18.5 Scores on a scale | Standard Error 0.9 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | MADRS | -19.4 Scores on a scale | Standard Error 0.9 |
p-value: <0.000195% CI: [-7.98, -3.11]ANCOVA
p-value: <0.000195% CI: [-7.53, -2.66]ANCOVA
p-value: <0.000195% CI: [-8.43, -3.56]ANCOVA
Secondary
SDS: Social Subscale
The SDS comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment.
Time frame: Mean change from baseline to Week 8
Population: Mean change from baseline to Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | SDS: Social Subscale | -2.7 Scores on a scale | Standard Error 0.03 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | SDS: Social Subscale | -3.9 Scores on a scale | Standard Error 0.02 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | SDS: Social Subscale | -3.8 Scores on a scale | Standard Error 0.02 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | SDS: Social Subscale | -4.1 Scores on a scale | Standard Error 0.02 |
p-value: 0.000295% CI: [-1.82, -0.58]ANCOVA
p-value: 0.000695% CI: [-1.72, -0.48]ANCOVA
p-value: <0.000195% CI: [-2, -0.76]ANCOVA
Secondary
SDS: Work Subscale
The SDS comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment.
Time frame: Mean change from baseline to Week 8
Population: Mean change from baseline to Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | SDS: Work Subscale | -2.7 Scores on a scale | Standard Error 0.03 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | SDS: Work Subscale | -3.8 Scores on a scale | Standard Error 0.02 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | SDS: Work Subscale | -3.8 Scores on a scale | Standard Error 0.02 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | SDS: Work Subscale | -4.0 Scores on a scale | Standard Error 0.02 |
p-value: 0.000795% CI: [-1.72, -0.46]ANCOVA
p-value: 0.001395% CI: [-1.69, -0.41]ANCOVA
p-value: <0.000195% CI: [-1.92, -0.66]ANCOVA
Secondary
Sheehan Disability Scale (SDS): Family Subscale
The SDS comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment.
Time frame: Mean change from baseline to Week 8
Population: Mean change from baseline to Week 8 (FAS, LOCF, ANCOVA)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Orally, Once Daily) | Sheehan Disability Scale (SDS): Family Subscale | -2.8 Scores on a scale | Standard Error 0.02 |
| Escitalopram 20 mg and Placebo (Orally, Once Daily) | Sheehan Disability Scale (SDS): Family Subscale | -4.0 Scores on a scale | Standard Error 0.02 |
| Escitalopram 20 mg and Gaboxadol 5 mg (Orally, Once Daily) | Sheehan Disability Scale (SDS): Family Subscale | -3.9 Scores on a scale | Standard Error 0.02 |
| Escitalopram 20 mg and Gaboxadol 10 mg (Orally, Once Daily) | Sheehan Disability Scale (SDS): Family Subscale | -4.1 Scores on a scale | Standard Error 0.02 |
p-value: <0.000195% CI: [-1.85, -0.64]ANCOVA
p-value: 0.000495% CI: [-1.72, -0.5]ANCOVA
p-value: <0.000195% CI: [-1.87, -0.65]ANCOVA