Trial Outcomes & Findings for Study of Pharmacotherapy of Psychotic Depression (NCT NCT00056472)

Last Updated: 2013-08-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

259 participants

Primary outcome timeframe

Weeks 1 to 12

Results posted on

2013-08-02

Participant Flow

Subjects were recruited from the inpatient and outpatient services of four academic sites between December of 2002 and June of 2007.

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.

Participant milestones

Participant milestones
Measure	Sertraline Plus Olanzapine 50-200mg/day sertraline plus 5-20mg/day olanzapine	Olanzapine Plus Placebo 5-20mg/day olanzapine plus placebo
Overall Study STARTED	129	130
Overall Study COMPLETED	81	61
Overall Study NOT COMPLETED	48	69

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Pharmacotherapy of Psychotic Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pharmacotherapy n=129 Participants sertraline plus olanzapine	Monotherapy n=130 Participants placebo plus olanzapine	Total n=259 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	77 Participants n=5 Participants	73 Participants n=7 Participants	150 Participants n=5 Participants
Age, Categorical >=65 years	52 Participants n=5 Participants	56 Participants n=7 Participants	108 Participants n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	83 Participants n=7 Participants	166 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	47 Participants n=7 Participants	93 Participants n=5 Participants
Region of Enrollment United States	89 participants n=5 Participants	89 participants n=7 Participants	178 participants n=5 Participants
Region of Enrollment Canada	40 participants n=5 Participants	41 participants n=7 Participants	81 participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 1 to 12

Outcome measures

Outcome measures
Measure	Pharmacotherapy n=124 Participants sertraline plus olanzapine	Monotherapy n=126 Participants placebo plus olanzapine
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	31 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pharmacotherapy n=124 Participants sertraline plus olanzapine	Monotherapy n=126 Participants placebo plus olanzapine
Scores on CGI-S Compared to Baseline Over the Course of the Trial	2.24 units on CGI scale Standard Error .07	2.48 units on CGI scale Standard Error .07

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pharmacotherapy n=124 Participants sertraline plus olanzapine	Monotherapy n=125 Participants placebo plus olanzapine
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 .61	16.63 Scores on Ham-D Standard Error .61

Adverse Events

Pharmacotherapy

Serious events: 9 serious events

Other events: 39 other events

Deaths: 0 deaths

Monotherapy

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pharmacotherapy n=129 participants at risk sertraline plus olanzapine	Monotherapy n=130 participants at risk placebo plus olanzapine
Psychiatric disorders worsening depression	7.0% 9/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	2.3% 3/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Respiratory, thoracic and mediastinal disorders pneumonia	0.78% 1/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	0.00% 0/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Musculoskeletal and connective tissue disorders broken hip	0.78% 1/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	0.00% 0/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Musculoskeletal and connective tissue disorders knee sepsis	0.00% 0/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	0.77% 1/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Vascular disorders chest pain	0.00% 0/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	0.77% 1/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders accidental overdose	0.00% 0/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	0.77% 1/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Vascular disorders leg pain/edema	0.78% 1/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	0.00% 0/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.

Other adverse events

Other adverse events
Measure	Pharmacotherapy n=129 participants at risk sertraline plus olanzapine	Monotherapy n=130 participants at risk placebo plus olanzapine
Metabolism and nutrition disorders weight gain	30.2% 39/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	26.9% 35/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders fall	19.4% 25/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	12.3% 16/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders sleepiness/sedation	7.0% 9/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	8.5% 11/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Metabolism and nutrition disorders increased lab values	10.9% 14/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	2.3% 3/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders reduced sleep	3.1% 4/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	5.4% 7/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Vascular disorders pedal edema/edema	5.4% 7/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	1.5% 2/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders Increased fatigability	1.6% 2/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	5.4% 7/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders increased sleep	3.1% 4/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	3.1% 4/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders increased dream activity	5.4% 7/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	0.77% 1/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Gastrointestinal disorders constipation	2.3% 3/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	3.1% 4/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
General disorders dizziness/feeling faint	3.9% 5/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	1.5% 2/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Nervous system disorders akathisia	0.00% 0/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	5.4% 7/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Gastrointestinal disorders nausea/vomiting	1.6% 2/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	3.1% 4/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.
Nervous system disorders tremor	0.78% 1/129 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.	3.8% 5/130 • Subjects participated for a maximum of 12 weeks. Study duration of 4.5 years 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.

Additional Information

Barnett S. Meyers, MD

Weill Cornell Medical College

Phone: 914-997-5721

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place