Major Depressive Disorder
Conditions
Keywords
Unipolar
Brief summary
The purpose of this study was to demonstrate efficacy, safety and clinical benefit of Trazodone Contramid® OAD (Once A Day) in the treatment of Unipolar Major Depressive Disorder (MDD).
Detailed description
This two-arm, multicentre, randomized, placebo-controlled, double-blind, parallel-design study consisted of a baseline phase (screening and wash-out) and a double-blind randomized phase (randomization to Trazodone Contramid® OAD or placebo). The total study duration including wash-out of prohibited medications was approximately 11 weeks; the total duration of the randomized phase was 8 weeks (titration: 2 weeks + treatment: 6 weeks).
Interventions
DRUGTrazodone Hydrochloride (HCl) Extended-Release Tablets
DRUGPlacebo
Sponsors
Labopharm Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females. * Aged 18 years or older. * Fulfills Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for Unipolar Major Depressive Disorder (MDD) (Axis I) as confirmed by the Mini-International Neuropsychiatric Interview (MINI). * The primary DSM-IV Axis I diagnosis should be MDD (296.22, 296.23, 296.32, 296.33); any subject meeting criteria for another, non excluded Axis I disorder, must demonstrate MDD as the primary disorder. * The current episode of MDD should have lasted for a minimum of 1 month, whether the patient has been diagnosed with one single or recurrent episodes. * Presence of dysphoria for most days over the past four weeks. * Montgomery-Åsberg Depression Rating Scale (MADRS) total score of at least 26 at screening and baseline. * Oral and written language comprehension at a level sufficient to comply with the protocol and to complete study-related materials. * Sign and date a written Informed Consent Form (ICF) approved by a Research Ethic Board (REB) which has also been signed and dated by the Investigator prior to study participation.
Exclusion criteria
* DSM-IV Major Depressive Disorder Specifiers: \[a\] With Catatonic Features; \[b\] With Postpartum Onset; \[c\] With Seasonal Pattern; * Presence of any of the following DSM-IV Axis I disorders: generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, eating disorder, bipolar disorder, alcohol/substance abuse or dependence (caffeine and nicotine allowed), any psychotic disorder. * Depression secondary to stroke, cancer or other severe medical illnesses. * Positive urine drug screen at screening visit. * History or present condition of any DSM-IV Axis II disorder. * History of treatment refractory major depressive episodes defined as incomplete or no therapeutic response to two prior courses of at least one month of conventional antidepressant drug treatment in adequate dosages. * Currently in psychotherapy (at least one session in the past month with a plan for continuing) with a licensed/registered/certified mental health provider, marriage counselor, or family therapist. * Meet criteria for high suicide risk on the MINI suicide scale, or in the opinion of the investigator is inappropriate for the trial due to clinically significant suicidal or homicidal potential. * Require hospitalization for treatment of the current episode of depression. * Uncorrected hypo- or hyperthyroidism. * A history of seizures other than pediatric febrile seizure. * A history of cardiac arrythmias requiring therapy. * A history of myocardial infarction within 1 year before screening. * Clinically significant abnormal findings of Electrocardiography (ECG), laboratory parameters. * Unwilling to discontinue use of any antidepressants, including herbal remedies, for a minimum of 5 drug half-lives prior to screening. * Unwilling to discontinue use of prohibited medications for a minimum of 5 drug half-lives prior to screening. * Treatment within the last 3 weeks with Monoamine Oxidase (MAO) inhibitors. * Use of the following concomitant treatment during the study: * medications causing QT prolongation (e.g. amiodarone, droperidol, erythromycin). * medications causing PR prolongation (e.g. digoxin). * Anti -psychotics (e.g. haloperidol). * protease inhibitors such as ritonavir and indinavir. * Hormonal treatment (e.g. estrogen, oral contraceptives) which has started within 3 months of study entry. * Treatment with another investigational agent within the last 30 days. * Known and documented allergy to trazodone or any structurally similar drugs. * Previous failure of treatment with trazodone, or previous discontinuation of treatment with trazodone due to Adverse Events. * Bowel disease causing malabsorption. * Serious, unstable illnesses during the 3 months before screening including but not limited to: hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic or hematological disease. * Pregnant or lactating, or is of childbearing potential and not willing to use an approved method of contraception. * Significant liver disease, defined as active hepatitis or elevated liver enzymes \>3 times the upper boundary of the normal range. * Significant renal disease, defined as Blood Urea Nitrogen (BUN) and/or creatinine \>3 times the upper boundary of the normal range clearance. * Any other condition that, in the opinion of the investigators, would adversely affect the patient's ability to complete the study or its measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline | Baseline to Week 8 | The Hamilton Depression Rating Scale 17 items \[HAMD-17\] is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17score ranges from 0 (not ill) to 52 (severely ill). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HAMD-17 Remitters at Each Visit | Weeks 1, 2, 3, 4, 6, 8 | Number of patients who are remitters (defined as patients who achieved a HAMD-17 total score ≤7) at each post-baseline visit. |
| Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Baseline to Weeks 1, 2, 3, 4, 6, 8 | Change from baseline in the HAMD-17, item 1: Depressed Mood item, at each post-baseline visit. The Depressed Mood item is rated on a 5-point scale ranging from rating of 0=absent; to 4=very severe. |
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Baseline to Week 8 | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10 item clinician-administered depression rating scale. The 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts) are rated on a scale ranging from 0 (low severity/difficulty) to 6 (high severity/difficulty) with anchors at 2-point intervals. The overall total score range is from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Baseline to Weeks 1, 2, 3, 4, 6, 8 | The CGI-Severity (CGI-S) consists of one question for the investigator: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated on the following seven-point scale: 1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. |
| Clinical Global Impression - Improvement of Illness (CGI-I) Score at Last Study Visit | Week 8 | The CGI-Improvement of Illness (CGI-I) consists of one question for the investigator: Compared to his condition at the start of the study, how much has this patient changed? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse. |
| Patient Global Impression - Improvement of Illness (PGI-I) Score at Last Study Visit | Week 8 | The PGI-Improvement of Illness (PGI-I) consists of one question for the patient: Since the start of the study, my overall status with regard to depression is? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse. |
| HAMD-17 Responders at Each Visit | Weeks 1, 2, 3, 4, 6, 8 | Number of patients who show a response (defined as at least a 50% reduction from baseline in HAMD-17 score) at each post-baseline visit. |
| Patient Global Impression - Improvement of Illness (PGI-I) Responders at Last Study Visit | Week 8 | Patients were responders if the PGI-I rating was Much Improved or Very Much Improved. The PGI-Improvement of Illness (PGI-I) consists of one question for the patient: Since the start of the study, my overall status with regard to depression is? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse. Results are expressed in number of patients. |
| Overall Quality of Sleep at Each Visit | Weeks 1, 2, 3, 4, 6, 8 | Overall Quality of Sleep was measured on a 4-point rating scale ranging from 1 = very poor to 4 = excellent in response to the question: Since the last study visit, how would you rate the overall quality of your sleep?. |
| Trouble Falling Asleep at Each Visit | Weeks 1, 2, 3, 4, 6, 8 | Trouble Falling Asleep was measured on a 4-point rating scale ranging from 1 = never to 4 = always in response to the question: Since the last study visit, how often did you experience trouble falling asleep?. |
| Awakening During the Night at Each Visit | Weeks 1, 2, 3, 4, 6, 8 | Awakening during the night was measured on a 4-point rating scale ranging from 1 = never to 4 = always in response to the question: Since the last study visit did you awaken during the night?. |
| Discontinuation Due to Lack of Efficacy | Baseline to Week 8 | Number of patients who discontinued due to lack of efficacy during the whole study period (8 weeks). |
| Clinical Global Impression - Improvement of Illness (CGI-I) Responders at Last Study Visit | Week 8 | Patients were responders if the CGI-I rating was Much Improved or Very Much Improved. The CGI-Improvement of Illness (CGI-I) consists of one question for the investigator: Compared to his condition at the start of the study, how much has this patient changed? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse. Results are expressed in number of patients. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trazodone Contramid OAD Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability. | 202 |
| Placebo Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD. | 204 |
| Total | 406 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason | 2 | 0 |
| Overall Study | Adverse Event | 25 | 6 |
| Overall Study | Entered other study | 1 | 0 |
| Overall Study | Lack of Efficacy | 8 | 9 |
| Overall Study | Lost to Follow-up | 11 | 15 |
| Overall Study | Noncompliance | 4 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 9 |
Baseline characteristics
| Characteristic | Trazodone Contramid OAD | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical >=65 years | 9 Participants | 16 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 193 Participants | 186 Participants | 379 Participants |
| Age Continuous | 43.8 years STANDARD_DEVIATION 12.83 | 44.0 years STANDARD_DEVIATION 13.45 | 43.9 years STANDARD_DEVIATION 13.12 |
| Region of Enrollment Canada | 33 participants | 38 participants | 71 participants |
| Region of Enrollment United States | 169 participants | 166 participants | 335 participants |
| Sex: Female, Male Female | 129 Participants | 131 Participants | 260 Participants |
| Sex: Female, Male Male | 73 Participants | 73 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 168 / 202 | 122 / 204 |
| serious Total, serious adverse events | 4 / 202 | 2 / 204 |
Outcome results
Primary
Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline
The Hamilton Depression Rating Scale 17 items \[HAMD-17\] is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17score ranges from 0 (not ill) to 52 (severely ill).
Time frame: Baseline to Week 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Week 8 Last Observation Carried Forward (LOCF): Trazodone = 202, placebo = 204.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trazodone Contramid OAD | Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline | Baseline | 23.2 Points on HAMD-17 scale | Standard Deviation 4.16 |
| Trazodone Contramid OAD | Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline | Week 8 or LOCF | 11.8 Points on HAMD-17 scale | Standard Deviation 7.99 |
| Trazodone Contramid OAD | Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline | Change from baseline | -11.4 Points on HAMD-17 scale | Standard Deviation 8.2 |
| Placebo | Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline | Week 8 or LOCF | 13.2 Points on HAMD-17 scale | Standard Deviation 8.06 |
| Placebo | Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline | Baseline | 22.4 Points on HAMD-17 scale | Standard Deviation 4.43 |
| Placebo | Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline | Change from baseline | -9.3 Points on HAMD-17 scale | Standard Deviation 7.94 |
Comparison: The primary null hypothesis for the HAMD-17 total score is that there is no difference between the Trazodone Contramid® OAD group and the placebo group at Week 8. A sample size of 133 in each group will have 90% power to detect a difference in the absolute mean Hamilton Rating Scale for Depression (HAMD-17) change from baseline of 3.0 units assuming that the common standard deviation is 7.5 using a two-group t-test with a 0.05 two-sided significance level.p-value: 0.0119ANCOVA
Secondary
Awakening During the Night at Each Visit
Awakening during the night was measured on a 4-point rating scale ranging from 1 = never to 4 = always in response to the question: Since the last study visit did you awaken during the night?.
Time frame: Weeks 1, 2, 3, 4, 6, 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trazodone Contramid OAD | Awakening During the Night at Each Visit | Score at Week 8 (n=201, n=204) | 2.2 Units on a scale | Standard Deviation 0.89 |
| Trazodone Contramid OAD | Awakening During the Night at Each Visit | Score at Baseline (n=202, n=204) | 3.2 Units on a scale | Standard Deviation 0.78 |
| Trazodone Contramid OAD | Awakening During the Night at Each Visit | Score at Week 1 (n=196, n=199) | 2.4 Units on a scale | Standard Deviation 0.96 |
| Trazodone Contramid OAD | Awakening During the Night at Each Visit | Score at Week 2 (n=200, n=203) | 2.4 Units on a scale | Standard Deviation 0.94 |
| Trazodone Contramid OAD | Awakening During the Night at Each Visit | Score at Week 3 (n=201, n=204) | 2.2 Units on a scale | Standard Deviation 0.91 |
| Trazodone Contramid OAD | Awakening During the Night at Each Visit | Score at Week 4 (n=201, n=204) | 2.2 Units on a scale | Standard Deviation 0.89 |
| Trazodone Contramid OAD | Awakening During the Night at Each Visit | Score at Week 6 (n=201, n=204) | 2.2 Units on a scale | Standard Deviation 0.94 |
| Placebo | Awakening During the Night at Each Visit | Score at Week 8 (n=201, n=204) | 2.5 Units on a scale | Standard Deviation 0.95 |
| Placebo | Awakening During the Night at Each Visit | Score at Week 3 (n=201, n=204) | 2.6 Units on a scale | Standard Deviation 0.9 |
| Placebo | Awakening During the Night at Each Visit | Score at Baseline (n=202, n=204) | 3.2 Units on a scale | Standard Deviation 0.78 |
| Placebo | Awakening During the Night at Each Visit | Score at Week 6 (n=201, n=204) | 2.5 Units on a scale | Standard Deviation 0.95 |
| Placebo | Awakening During the Night at Each Visit | Score at Week 1 (n=196, n=199) | 2.7 Units on a scale | Standard Deviation 0.85 |
| Placebo | Awakening During the Night at Each Visit | Score at Week 4 (n=201, n=204) | 2.6 Units on a scale | Standard Deviation 0.93 |
| Placebo | Awakening During the Night at Each Visit | Score at Week 2 (n=200, n=203) | 2.5 Units on a scale | Standard Deviation 0.92 |
Secondary
Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
The CGI-Severity (CGI-S) consists of one question for the investigator: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated on the following seven-point scale: 1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.
Time frame: Baseline to Weeks 1, 2, 3, 4, 6, 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trazodone Contramid OAD | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 4 (n=202, n=204) | -1.6 Units on CGI-S scale | Standard Deviation 1.22 |
| Trazodone Contramid OAD | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 2 (n=201, n=203) | -1.0 Units on CGI-S scale | Standard Deviation 1.02 |
| Trazodone Contramid OAD | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 6 (n=202, n=204) | -1.7 Units on CGI-S scale | Standard Deviation 1.24 |
| Trazodone Contramid OAD | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 3 (n=202, n=204) | -1.4 Units on CGI-S scale | Standard Deviation 1.16 |
| Trazodone Contramid OAD | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 8 (n=202, n=204) | -1.7 Units on CGI-S scale | Standard Deviation 1.36 |
| Trazodone Contramid OAD | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 1 (n=197, n=199) | -0.6 Units on CGI-S scale | Standard Deviation 0.72 |
| Placebo | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 8 (n=202, n=204) | -1.4 Units on CGI-S scale | Standard Deviation 1.37 |
| Placebo | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 1 (n=197, n=199) | -0.5 Units on CGI-S scale | Standard Deviation 0.75 |
| Placebo | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 3 (n=202, n=204) | -1.1 Units on CGI-S scale | Standard Deviation 1.12 |
| Placebo | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 4 (n=202, n=204) | -1.3 Units on CGI-S scale | Standard Deviation 1.17 |
| Placebo | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 6 (n=202, n=204) | -1.4 Units on CGI-S scale | Standard Deviation 1.24 |
| Placebo | Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit | Change in CGI-S score at Week 2 (n=201, n=203) | -0.8 Units on CGI-S scale | Standard Deviation 0.98 |
Secondary
Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
Change from baseline in the HAMD-17, item 1: Depressed Mood item, at each post-baseline visit. The Depressed Mood item is rated on a 5-point scale ranging from rating of 0=absent; to 4=very severe.
Time frame: Baseline to Weeks 1, 2, 3, 4, 6, 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trazodone Contramid OAD | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 2 (n=201, n=203) | -1.1 Points on the HAMD scale | Standard Deviation 1.13 |
| Trazodone Contramid OAD | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 4 (n=202, n=204) | -1.5 Points on the HAMD scale | Standard Deviation 1.21 |
| Trazodone Contramid OAD | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 1 (n=197, n=199) | -0.7 Points on the HAMD scale | Standard Deviation 0.89 |
| Trazodone Contramid OAD | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 6 (n=202, n=204) | -1.5 Points on the HAMD scale | Standard Deviation 1.18 |
| Trazodone Contramid OAD | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 3 (n=202, n=204) | -1.4 Points on the HAMD scale | Standard Deviation 1.18 |
| Trazodone Contramid OAD | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 8 (n=202, n=204) | -1.6 Points on the HAMD scale | Standard Deviation 1.29 |
| Placebo | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 3 (n=202, n=204) | -1.0 Points on the HAMD scale | Standard Deviation 1.08 |
| Placebo | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 1 (n=197, n=199) | -0.5 Points on the HAMD scale | Standard Deviation 0.74 |
| Placebo | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 2 (n=201, n=203) | -0.8 Points on the HAMD scale | Standard Deviation 0.95 |
| Placebo | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 8 (n=202, n=204) | -1.3 Points on the HAMD scale | Standard Deviation 1.22 |
| Placebo | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 4 (n=202, n=204) | -1.2 Points on the HAMD scale | Standard Deviation 1.12 |
| Placebo | Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit | Change in score at Week 6 (n=202, n=204) | -1.3 Points on the HAMD scale | Standard Deviation 1.15 |
Secondary
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10 item clinician-administered depression rating scale. The 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts) are rated on a scale ranging from 0 (low severity/difficulty) to 6 (high severity/difficulty) with anchors at 2-point intervals. The overall total score range is from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline to Week 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. MADRS Week 8 Observed Cases: Trazodone = 178, placebo = 182.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trazodone Contramid OAD | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Baseline (n=202, n=204) | 32.6 Units on MADRS scale | Standard Deviation 4.07 |
| Trazodone Contramid OAD | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Week 8 (n=178, n=182) | 16.0 Units on MADRS scale | Standard Deviation 11.24 |
| Trazodone Contramid OAD | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change from baseline (n=178, n=182) | -16.6 Units on MADRS scale | Standard Deviation 11.27 |
| Placebo | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Baseline (n=202, n=204) | 31.9 Units on MADRS scale | Standard Deviation 4.33 |
| Placebo | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Week 8 (n=178, n=182) | 17.7 Units on MADRS scale | Standard Deviation 11.62 |
| Placebo | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change from baseline (n=178, n=182) | -14.1 Units on MADRS scale | Standard Deviation 11.27 |
Secondary
Clinical Global Impression - Improvement of Illness (CGI-I) Responders at Last Study Visit
Patients were responders if the CGI-I rating was Much Improved or Very Much Improved. The CGI-Improvement of Illness (CGI-I) consists of one question for the investigator: Compared to his condition at the start of the study, how much has this patient changed? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse. Results are expressed in number of patients.
Time frame: Week 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. CGI-I Responders Week 8 Observed Cases: Trazodone = 180, placebo = 183.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trazodone Contramid OAD | Clinical Global Impression - Improvement of Illness (CGI-I) Responders at Last Study Visit | 96 participants |
| Placebo | Clinical Global Impression - Improvement of Illness (CGI-I) Responders at Last Study Visit | 89 participants |
Secondary
Clinical Global Impression - Improvement of Illness (CGI-I) Score at Last Study Visit
The CGI-Improvement of Illness (CGI-I) consists of one question for the investigator: Compared to his condition at the start of the study, how much has this patient changed? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse.
Time frame: Week 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. CGI-I Week 8 Observed Cases: Trazodone = 178, placebo = 182.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trazodone Contramid OAD | Clinical Global Impression - Improvement of Illness (CGI-I) Score at Last Study Visit | 2.4 Units on the CGI-I scale | Standard Deviation 1.23 |
| Placebo | Clinical Global Impression - Improvement of Illness (CGI-I) Score at Last Study Visit | 2.5 Units on the CGI-I scale | Standard Deviation 1.32 |
Secondary
Discontinuation Due to Lack of Efficacy
Number of patients who discontinued due to lack of efficacy during the whole study period (8 weeks).
Time frame: Baseline to Week 8
Population: Safety population is defined as all randomized patients who received any study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trazodone Contramid OAD | Discontinuation Due to Lack of Efficacy | 8 participants |
| Placebo | Discontinuation Due to Lack of Efficacy | 9 participants |
Secondary
HAMD-17 Remitters at Each Visit
Number of patients who are remitters (defined as patients who achieved a HAMD-17 total score ≤7) at each post-baseline visit.
Time frame: Weeks 1, 2, 3, 4, 6, 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trazodone Contramid OAD | HAMD-17 Remitters at Each Visit | Number of remitters at Week 1 (n=197, n=199) | 10 Participants |
| Trazodone Contramid OAD | HAMD-17 Remitters at Each Visit | Number of remitters at Week 2 (n=201, n=203) | 29 Participants |
| Trazodone Contramid OAD | HAMD-17 Remitters at Each Visit | Number of remitters at Week 3 (n=202, n=204) | 51 Participants |
| Trazodone Contramid OAD | HAMD-17 Remitters at Each Visit | Number of remitters at Week 4 (n=202, n=204) | 61 Participants |
| Trazodone Contramid OAD | HAMD-17 Remitters at Each Visit | Number of remitters at Week 6 (n=202, n=204) | 66 Participants |
| Trazodone Contramid OAD | HAMD-17 Remitters at Each Visit | Number of remitters at Week 8 (n=202, n=204) | 72 Participants |
| Placebo | HAMD-17 Remitters at Each Visit | Number of remitters at Week 6 (n=202, n=204) | 47 Participants |
| Placebo | HAMD-17 Remitters at Each Visit | Number of remitters at Week 1 (n=197, n=199) | 9 Participants |
| Placebo | HAMD-17 Remitters at Each Visit | Number of remitters at Week 4 (n=202, n=204) | 43 Participants |
| Placebo | HAMD-17 Remitters at Each Visit | Number of remitters at Week 2 (n=201, n=203) | 24 Participants |
| Placebo | HAMD-17 Remitters at Each Visit | Number of remitters at Week 8 (n=202, n=204) | 65 Participants |
| Placebo | HAMD-17 Remitters at Each Visit | Number of remitters at Week 3 (n=202, n=204) | 32 Participants |
Secondary
HAMD-17 Responders at Each Visit
Number of patients who show a response (defined as at least a 50% reduction from baseline in HAMD-17 score) at each post-baseline visit.
Time frame: Weeks 1, 2, 3, 4, 6, 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trazodone Contramid OAD | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 1 (n=197, n=199) | 25 Participants |
| Trazodone Contramid OAD | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 2 (n=201, n=203) | 63 Participants |
| Trazodone Contramid OAD | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 3 (n=202, n=204) | 89 Participants |
| Trazodone Contramid OAD | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 4 (n=202, n=204) | 95 Participants |
| Trazodone Contramid OAD | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 6 (n=202, n=204) | 100 Participants |
| Trazodone Contramid OAD | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 8 (n=202, n=204) | 109 Participants |
| Placebo | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 6 (n=202, n=204) | 81 Participants |
| Placebo | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 1 (n=197, n=199) | 19 Participants |
| Placebo | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 4 (n=202, n=204) | 74 Participants |
| Placebo | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 2 (n=201, n=203) | 41 Participants |
| Placebo | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 8 (n=202, n=204) | 84 Participants |
| Placebo | HAMD-17 Responders at Each Visit | ≥50% reduction in HAMD-17 at Week 3 (n=202, n=204) | 53 Participants |
Secondary
Overall Quality of Sleep at Each Visit
Overall Quality of Sleep was measured on a 4-point rating scale ranging from 1 = very poor to 4 = excellent in response to the question: Since the last study visit, how would you rate the overall quality of your sleep?.
Time frame: Weeks 1, 2, 3, 4, 6, 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trazodone Contramid OAD | Overall Quality of Sleep at Each Visit | Score at Week 1 (n=196, n=199) | 0.7 Points on a scale | Standard Deviation 0.9 |
| Trazodone Contramid OAD | Overall Quality of Sleep at Each Visit | Score at Week 4 (n=201, n=204) | 1.0 Points on a scale | Standard Deviation 1.02 |
| Trazodone Contramid OAD | Overall Quality of Sleep at Each Visit | Score at Baseline (n=202, n=204) | 1.6 Points on a scale | Standard Deviation 0.65 |
| Trazodone Contramid OAD | Overall Quality of Sleep at Each Visit | Score at Week 6 (n=201, n=204) | 1.0 Points on a scale | Standard Deviation 1.01 |
| Trazodone Contramid OAD | Overall Quality of Sleep at Each Visit | Score at Week 2 (n=200, n=203) | 0.8 Points on a scale | Standard Deviation 0.97 |
| Trazodone Contramid OAD | Overall Quality of Sleep at Each Visit | Score at Week 8 (n=201, n=204) | 1.0 Points on a scale | Standard Deviation 1.05 |
| Trazodone Contramid OAD | Overall Quality of Sleep at Each Visit | Score at Week 3 (n=201, n=204) | 0.9 Points on a scale | Standard Deviation 1 |
| Placebo | Overall Quality of Sleep at Each Visit | Score at Week 8 (n=201, n=204) | 0.8 Points on a scale | Standard Deviation 1.1 |
| Placebo | Overall Quality of Sleep at Each Visit | Score at Baseline (n=202, n=204) | 1.6 Points on a scale | Standard Deviation 0.7 |
| Placebo | Overall Quality of Sleep at Each Visit | Score at Week 1 (n=196, n=199) | 0.4 Points on a scale | Standard Deviation 0.83 |
| Placebo | Overall Quality of Sleep at Each Visit | Score at Week 3 (n=201, n=204) | 0.7 Points on a scale | Standard Deviation 1 |
| Placebo | Overall Quality of Sleep at Each Visit | Score at Week 4 (n=201, n=204) | 0.7 Points on a scale | Standard Deviation 1.02 |
| Placebo | Overall Quality of Sleep at Each Visit | Score at Week 6 (n=201, n=204) | 0.9 Points on a scale | Standard Deviation 1.04 |
| Placebo | Overall Quality of Sleep at Each Visit | Score at Week 2 (n=200, n=203) | 0.7 Points on a scale | Standard Deviation 0.99 |
Secondary
Patient Global Impression - Improvement of Illness (PGI-I) Responders at Last Study Visit
Patients were responders if the PGI-I rating was Much Improved or Very Much Improved. The PGI-Improvement of Illness (PGI-I) consists of one question for the patient: Since the start of the study, my overall status with regard to depression is? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse. Results are expressed in number of patients.
Time frame: Week 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. PGI-I Responders Week 8 Observed Cases: Trazodone = 176, placebo = 183.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trazodone Contramid OAD | Patient Global Impression - Improvement of Illness (PGI-I) Responders at Last Study Visit | 90 participants |
| Placebo | Patient Global Impression - Improvement of Illness (PGI-I) Responders at Last Study Visit | 80 participants |
Secondary
Patient Global Impression - Improvement of Illness (PGI-I) Score at Last Study Visit
The PGI-Improvement of Illness (PGI-I) consists of one question for the patient: Since the start of the study, my overall status with regard to depression is? which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.
Time frame: Week 8
Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. PGI-I Week 8 Observed Cases: Trazodone = 176, placebo = 183.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trazodone Contramid OAD | Patient Global Impression - Improvement of Illness (PGI-I) Score at Last Study Visit | 2.6 Units on PGI-I scale | Standard Deviation 1.19 |
| Placebo | Patient Global Impression - Improvement of Illness (PGI-I) Score at Last Study Visit | 2.8 Units on PGI-I scale | Standard Deviation 1.35 |
Secondary
Trouble Falling Asleep at Each Visit
Trouble Falling Asleep was measured on a 4-point rating scale ranging from 1 = never to 4 = always in response to the question: Since the last study visit, how often did you experience trouble falling asleep?.
Time frame: Weeks 1, 2, 3, 4, 6, 8
Population: Full Analysis set (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trazodone Contramid OAD | Trouble Falling Asleep at Each Visit | Score at Week 2 (n=200, n=203) | 2.3 Units on a scale | Standard Deviation 0.93 |
| Trazodone Contramid OAD | Trouble Falling Asleep at Each Visit | Score at Week 4 (n=201, n=204) | 2.1 Units on a scale | Standard Deviation 0.89 |
| Trazodone Contramid OAD | Trouble Falling Asleep at Each Visit | Score at Week 1 (n=196, n=199) | 2.5 Units on a scale | Standard Deviation 1.02 |
| Trazodone Contramid OAD | Trouble Falling Asleep at Each Visit | Score at Week 6 (n=201, n=204) | 2.1 Units on a scale | Standard Deviation 0.89 |
| Trazodone Contramid OAD | Trouble Falling Asleep at Each Visit | Score at Week 3 (n=201, n=204) | 2.2 Units on a scale | Standard Deviation 0.9 |
| Trazodone Contramid OAD | Trouble Falling Asleep at Each Visit | Score at Week 8 (n=201, n=204) | 2.1 Units on a scale | Standard Deviation 0.85 |
| Trazodone Contramid OAD | Trouble Falling Asleep at Each Visit | Score at Baseline (n=202, n=204) | 3.0 Units on a scale | Standard Deviation 0.86 |
| Placebo | Trouble Falling Asleep at Each Visit | Score at Week 8 (n=201, n=204) | 2.3 Units on a scale | Standard Deviation 0.95 |
| Placebo | Trouble Falling Asleep at Each Visit | Score at Baseline (n=202, n=204) | 2.9 Units on a scale | Standard Deviation 0.91 |
| Placebo | Trouble Falling Asleep at Each Visit | Score at Week 1 (n=196, n=199) | 2.6 Units on a scale | Standard Deviation 0.98 |
| Placebo | Trouble Falling Asleep at Each Visit | Score at Week 2 (n=200, n=203) | 2.5 Units on a scale | Standard Deviation 0.96 |
| Placebo | Trouble Falling Asleep at Each Visit | Score at Week 3 (n=201, n=204) | 2.3 Units on a scale | Standard Deviation 0.99 |
| Placebo | Trouble Falling Asleep at Each Visit | Score at Week 4 (n=201, n=204) | 2.3 Units on a scale | Standard Deviation 0.95 |
| Placebo | Trouble Falling Asleep at Each Visit | Score at Week 6 (n=201, n=204) | 2.3 Units on a scale | Standard Deviation 0.95 |