Major Depressive Disorder With Psychotic Features
Conditions
Keywords
Major depressive disorder with psychotic features, Delusional Depression, Randomized Trial, Combination Treatment, SSRI, Atypical Antipsychotic
Brief summary
This study will determine the effectiveness of combining selective serotonin reuptake inhibitors (SSRIs) with antipsychotic medications in the treatment of psychotic depression.
Detailed description
Approximately 25% of people who are admitted to hospitals for depression suffer from psychotic depression. People with psychotic depression experience hallucinations,and, more commonly delusions, in addition to major depression. Psychotic experiences may be either congruent with the theme of depression or incongruent, without an apparent relationship to feeling depressed. This study will determine the effectiveness of combining a selective serotonin reuptake inhibitor (SSRI) with antipsychotic medication in the treatment of psychotic depression accompanied by at least one identifiable delusion. The study will also evaluate the difference in treatment response of young adults versus geriatric patients. This double-blind study will last a total of 12 weeks. Participants will be randomly assigned to receive either olanzapine, an atypical antipsychotic drug, combined with sertraline, an SSRI, or olanzapine alone. Following baseline assessments, study visits will occur weekly until Week 6, and then bi-weekly until Week 12. Participants who do not respond to either treatment may leave the study at any time. Participants who achieve either partial or full response may participate in an additional 20-week study.
Interventions
DRUGOlanzapine
10-20mg/day
DRUGSertraline
150-200mg/day
OTHERplacebo
tablet that ressembles sertraline but contains no medication
Sponsors
National Institute of Mental Health (NIMH)
Weill Medical College of Cornell University
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
* Major depressive disorder, single or recurrent, with psychotic features
Exclusion criteria
* History of substance abuse or dependence within the 3 months prior to enrollment * Acute or unstable medical illness * Diagnosis of schizophrenia or other psychotic disorders * Pregnant * Intolerance to SSRIs or olanzapine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission of Depression Hamilton Depression Scale (Ham-D) and Psychosis Schedule for Affective Disorders in Schizophrenia - Delusional Item (SADS) During the Course of the Trial | Weeks 1 to 12 | Remission was defined as scores on Ham-D of less than 10 at two consecutive assessments and the absence of delusions (measured as SADS delusional item scores of 1) at the second assessment of the two-assessment remission of depression interval. Scores on Ham-D range from 0 to 52 with higher scores indicating more severe depression. Scores on SADS range from 1 to 7 with higher scores indicating the delusions(s) more adversely effect the subject's behavior. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Scores on CGI-S Compared to Baseline Over the Course of the Trial | Weeks 1 to 12 | A measure of overall symptom severity, the Clinical Global Impressions, Severity of Illness Scale (CGI-S). It is a seven point scale with a one indicating not at all ill, and seven indicating the most extremely ill. This rating was done each week after baseline by the PI at each site after visiting with the patient. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Score Hamilton Depression Rating Scale (Ham-D) Over the Course of the Trial From Week to Week. | Weeks 1 to 12 | The Ham-D measures depression severity. Scores on Ham-D range from 0 to 52 with higher scores indicating more severe depression. |
Countries
Canada, United States
Participant flow
Recruitment details
Subjects were recruited from the inpatient and outpatient services of four academic sites between December of 2002 and June of 2007.
Pre-assignment details
Antidepressant and antipsychotic medications being taken at entry were tapered and discontinued prior to randomization. Consented subjects were required to meet criteria for unipolar major depression and have at least one delusion. Subjects were also excluded if an unstable medical condition or evidence of recent substance abuse were present.
Participants by arm
| Arm | Count |
|---|---|
| Pharmacotherapy sertraline plus olanzapine | 129 |
| Monotherapy placebo plus olanzapine | 130 |
| Total | 259 |
Baseline characteristics
| Characteristic | Pharmacotherapy | Monotherapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 52 Participants | 56 Participants | 108 Participants |
| Age, Categorical Between 18 and 65 years | 77 Participants | 73 Participants | 150 Participants |
| Region of Enrollment Canada | 40 participants | 41 participants | 81 participants |
| Region of Enrollment United States | 89 participants | 89 participants | 178 participants |
| Sex: Female, Male Female | 83 Participants | 83 Participants | 166 Participants |
| Sex: Female, Male Male | 46 Participants | 47 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 39 / 129 | 35 / 130 |
| serious Total, serious adverse events | 9 / 129 | 3 / 130 |
Outcome results
Primary
Remission of Depression Hamilton Depression Scale (Ham-D) and Psychosis Schedule for Affective Disorders in Schizophrenia - Delusional Item (SADS) During the Course of the Trial
Remission was defined as scores on Ham-D of less than 10 at two consecutive assessments and the absence of delusions (measured as SADS delusional item scores of 1) at the second assessment of the two-assessment remission of depression interval. Scores on Ham-D range from 0 to 52 with higher scores indicating more severe depression. Scores on SADS range from 1 to 7 with higher scores indicating the delusions(s) more adversely effect the subject's behavior.
Time frame: Weeks 1 to 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pharmacotherapy | Remission of Depression Hamilton Depression Scale (Ham-D) and Psychosis Schedule for Affective Disorders in Schizophrenia - Delusional Item (SADS) During the Course of the Trial | 54 participants |
| Monotherapy | Remission of Depression Hamilton Depression Scale (Ham-D) and Psychosis Schedule for Affective Disorders in Schizophrenia - Delusional Item (SADS) During the Course of the Trial | 31 participants |
Comparison: Predicting remission rates of 40% in combination therapy and 20% in monotherapy subjects, 260 subjects randomized into the two treatment groups would provide \>80% power at a two-tailed alpha level of .05. Treatment efficacy was compared between groups based on intent-to-treat analyses for the longitudinal binary outcome of remission using mixed effects logistic regression with a random intercept that included treatment and time as fixed effects and a treatment by time interaction effect.p-value: <0.00195% CI: [1.12, 1.47]Regression, Logistic
Secondary
Scores on CGI-S Compared to Baseline Over the Course of the Trial
A measure of overall symptom severity, the Clinical Global Impressions, Severity of Illness Scale (CGI-S). It is a seven point scale with a one indicating not at all ill, and seven indicating the most extremely ill. This rating was done each week after baseline by the PI at each site after visiting with the patient.
Time frame: Weeks 1 to 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pharmacotherapy | Scores on CGI-S Compared to Baseline Over the Course of the Trial | 2.24 units on CGI scale | Standard Error 0.07 |
| Monotherapy | Scores on CGI-S Compared to Baseline Over the Course of the Trial | 2.48 units on CGI scale | Standard Error 0.07 |
Comparison: Intent-to-treat changes in global improvement from week to week compared to baseline (CGI-S) over the course of the trial using longitudinal mixed effects linear regression models. The null hypothesis is that there is no difference in overall change in CGI-S.p-value: 0.02Mixed Models Analysis
Other Pre-specified
Mean Score Hamilton Depression Rating Scale (Ham-D) Over the Course of the Trial From Week to Week.
The Ham-D measures depression severity. Scores on Ham-D range from 0 to 52 with higher scores indicating more severe depression.
Time frame: Weeks 1 to 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pharmacotherapy | Mean Score Hamilton Depression Rating Scale (Ham-D) Over the Course of the Trial From Week to Week. | 13.27 Scores on Ham-D | Standard Error 0.61 |
| Monotherapy | Mean Score Hamilton Depression Rating Scale (Ham-D) Over the Course of the Trial From Week to Week. | 16.63 Scores on Ham-D | Standard Error 0.61 |
Comparison: Intent-to-treat between group comparison using longitudinal mixed effects regression.p-value: <0.001Mixed Models Analysis