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Study of Pharmacotherapy of Psychotic Depression (STOP-PD)

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ClinicalTrials.gov Identifier: NCT00056472
Recruitment Status : Completed
First Posted : March 17, 2003
Results First Posted : August 2, 2013
Last Update Posted : August 2, 2013
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder With Psychotic Features
Interventions Drug: Olanzapine
Drug: Sertraline
Other: placebo
Enrollment 259
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.
Arm/Group Title Sertraline Plus Olanzapine Olanzapine Plus Placebo
Hide Arm/Group Description 50-200mg/day sertraline plus 5-20mg/day olanzapine 5-20mg/day olanzapine plus placebo
Period Title: Overall Study
Started 129 130
Completed 81 61
Not Completed 48 69
Arm/Group Title Pharmacotherapy Monotherapy Total
Hide Arm/Group Description sertraline plus olanzapine placebo plus olanzapine Total of all reporting groups
Overall Number of Baseline Participants 129 130 259
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 130 participants 259 participants
<=18 years
0
   0.0%
1
   0.8%
1
   0.4%
Between 18 and 65 years
77
  59.7%
73
  56.2%
150
  57.9%
>=65 years
52
  40.3%
56
  43.1%
108
  41.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 130 participants 259 participants
Female
83
  64.3%
83
  63.8%
166
  64.1%
Male
46
  35.7%
47
  36.2%
93
  35.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 130 participants 259 participants
United States 89 89 178
Canada 40 41 81
1.Primary Outcome
Title 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
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pharmacotherapy Monotherapy
Hide Arm/Group Description:
sertraline plus olanzapine
placebo plus olanzapine
Overall Number of Participants Analyzed 124 126
Measure Type: Number
Unit of Measure: participants
54 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pharmacotherapy, Monotherapy
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.28
Confidence Interval 95%
1.12 to 1.47
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Scores on CGI-S Compared to Baseline Over the Course of the Trial
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pharmacotherapy Monotherapy
Hide Arm/Group Description:
sertraline plus olanzapine
placebo plus olanzapine
Overall Number of Participants Analyzed 124 126
Mean (Standard Error)
Unit of Measure: units on CGI scale
2.24  (.07) 2.48  (.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pharmacotherapy, Monotherapy
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .02
Comments The p-value is for the overall mean CGI-S score compared to baseline.
Method Mixed Models Analysis
Comments This was a longitudinal analysis of CGI-S scores compared to baseline.
3.Other Pre-specified Outcome
Title Mean Score Hamilton Depression Rating Scale (Ham-D) Over the Course of the Trial From Week to Week.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pharmacotherapy Monotherapy
Hide Arm/Group Description:
sertraline plus olanzapine
placebo plus olanzapine
Overall Number of Participants Analyzed 124 125
Mean (Standard Error)
Unit of Measure: Scores on Ham-D
13.27  (.61) 16.63  (.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pharmacotherapy, Monotherapy
Comments Intent-to-treat between group comparison using longitudinal mixed effects regression.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments The p-value is for the overall mean across all time points between each treatment group.
Method Mixed Models Analysis
Comments [Not Specified]
Time Frame Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years
Adverse Event Reporting Description Extrapyramidal symptoms assessed using the Simpson Angus Scale, incident akathisia using the Barnes Akathisia Scale and tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale. Changes in UKU measured at each visit. Metabolic labs assessed monthly. Attrition. Other adverse events self-reported throughout study participation.
 
Arm/Group Title Pharmacotherapy Monotherapy
Hide Arm/Group Description sertraline plus olanzapine placebo plus olanzapine
All-Cause Mortality
Pharmacotherapy Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pharmacotherapy Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   9/129 (6.98%)   3/130 (2.31%) 
General disorders     
accidental overdose *  0/129 (0.00%)  1/130 (0.77%) 
Musculoskeletal and connective tissue disorders     
broken hip *  1/129 (0.78%)  0/130 (0.00%) 
knee sepsis *  0/129 (0.00%)  1/130 (0.77%) 
Psychiatric disorders     
worsening depression  [1]  9/129 (6.98%)  3/130 (2.31%) 
Respiratory, thoracic and mediastinal disorders     
pneumonia *  1/129 (0.78%)  0/130 (0.00%) 
Vascular disorders     
chest pain *  0/129 (0.00%)  1/130 (0.77%) 
leg pain/edema *  1/129 (0.78%)  0/130 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
worsening symptoms of depression requiring (re)hospitalization
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Pharmacotherapy Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   39/129 (30.23%)   35/130 (26.92%) 
Gastrointestinal disorders     
constipation   3/129 (2.33%)  4/130 (3.08%) 
nausea/vomiting   2/129 (1.55%)  4/130 (3.08%) 
General disorders     
fall   25/129 (19.38%)  16/130 (12.31%) 
sleepiness/sedation   9/129 (6.98%)  11/130 (8.46%) 
reduced sleep   4/129 (3.10%)  7/130 (5.38%) 
Increased fatigability   2/129 (1.55%)  7/130 (5.38%) 
increased sleep   4/129 (3.10%)  4/130 (3.08%) 
increased dream activity   7/129 (5.43%)  1/130 (0.77%) 
dizziness/feeling faint   5/129 (3.88%)  2/130 (1.54%) 
Metabolism and nutrition disorders     
weight gain   39/129 (30.23%)  35/130 (26.92%) 
increased lab values  [1]  14/129 (10.85%)  3/130 (2.31%) 
Nervous system disorders     
akathisia   0/129 (0.00%)  7/130 (5.38%) 
tremor   1/129 (0.78%)  5/130 (3.85%) 
Vascular disorders     
pedal edema/edema   7/129 (5.43%)  2/130 (1.54%) 
Indicates events were collected by systematic assessment
[1]
triglycerides, cholesterol, LFTs
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Barnett S. Meyers, MD
Organization: Weill Cornell Medical College
Phone: 914-997-5721
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00056472     History of Changes
Other Study ID Numbers: U01MH062624 ( U.S. NIH Grant/Contract )
U01MH062624 ( U.S. NIH Grant/Contract )
U01MH062565 ( U.S. NIH Grant/Contract )
U01MH062518 ( U.S. NIH Grant/Contract )
U01MH062446 ( U.S. NIH Grant/Contract )
First Submitted: March 14, 2003
First Posted: March 17, 2003
Results First Submitted: June 16, 2009
Results First Posted: August 2, 2013
Last Update Posted: August 2, 2013