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Sustaining Remission of Psychotic Depression (STOP-PD)

Primary Purpose

Psychotic Depression

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Sertraline + Olanzapine

Sertraline + Placebo

About this trial

This is an interventional treatment trial for Psychotic Depression

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Aged 18-85 years, inclusive
Diagnosis: Diagnostic Statistical Manual-IV Trade Revision (DSM IV-TR) non-bipolar major depression with psychotic features established by both clinical interview with research psychiatrist and administration of SCID-IV.
Score >2 on Schedule for Affective Disorders (SADS) delusion severity item
Score >1 on any of the three conviction items of the Delusion Assessment Scale (DAS) (does not alter belief in response to reality testing)
17-item HAM-D score of >20

Exclusion Criteria:

Current or lifetime DSM-IV-TR history of schizophrenia or other psychotic disorders or meeting current criteria for brief psychotic disorder, body dysmorphic disorder or obsessive-compulsive disorder
Current or lifetime DSM-IV-TR bipolar affective disorder
History of DSM-IV-TR defined alcohol or substance abuse or dependence within the past three months
Dementia or clinically significant cognitive impairment prior to index episode of depression, and/or a mean score >3 on 26-item caregiver assessment
Type 1 diabetes mellitus (defined as insulin-dependent diabetes mellitus with onset before age 35, and/or diabetes mellitus complicated by prior documented episode of ketoacidosis
Acute or unstable medical illness within the past 3 months; current abnormal serum free T4; current abnormally low vitamin B4 or folic acid level; medical conditions and/or medications for which psychotic or depressive symptoms can be a direct manifestation; neurological disease associated with extrapyramidal signs and symptoms; epilepsy, if the person has had one or more grand mal seizures within the past 12 months.
The need for treatment with any psychotropic medication other than sertraline, olanzapine or lorazepam; or with an anticonvulsant medication with mood-stabilizing properties.
Current pregnancy or plan to become pregnant during the course of the study; breast feeding in women with infants.
A documented history of being unable to tolerate olanzapine or sertraline including significant bradycardia (heart rate of <50 bpm), and serum sodium level of 129mmol/L or below.
History of non-response of the index episode of psychotic depression to at least a 6-week trial of at least 150mg/day sertraline combined with 15mg/day olanzapine
Patients showing ongoing improvement in current episode of psychotic depression with treatment other than sertraline or olanzapine
Patients who are in immediate need of electroconvulsive therapy (ECT) (imminent risk of suicide, refusing to eat, catatonic)

Sites / Locations

Anthony Rothschild, MD
George Alexopoulos, MD
Ellen Whyte, MD
Alastair Flint, MD

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sertraline + Olanzapine

Sertraline + Placebo

Arm Description

Randomized to continue with sertraline and olanzapine under double-blind conditions.

Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions.

Outcomes

Primary Outcome Measures

Number of Subjects at Risk of Relapse During the Randomized Phase.

Relapse criteria include at least one of the following: 1)Structured Clinical Interview for Diagnostic Statistical Manual #4 Trade Revision (DSM-IV-TR) Axis 1 Disorders (SCID) symptoms of major depression maintained over two weeks 2)17-item Hamilton Depression Rating Scale score of >17 maintained for more than one week + a mean increase of 5 points from entry into randomized phase 3)Re-emergence of psychosis for more than one week, with a SADS (Schedule for Affective Disorders and Schizophrenia) score of >2 on delusion or hallucination severity items 4)Significant clinical worsening defined as either emergence of high-risk of suicide, and/or development of mania for greater than one week, and/or psychiatric hospitalization.

Secondary Outcome Measures

Changes in Metabolic Measures: Weight

Change in weight from entry into randomized phase (baseline) and 36 weeks.

Changes in Metabolic Measure: Cholesterol

Change in cholesterol from entry into randomized phase (baseline) and 36 weeks.

Changes in Metabolic Measures: Triglycerides

Change in triglycerides from entry into randomized phase (baseline) and 36 weeks.

Full Information

NCT ID

NCT01427608

First Posted

August 30, 2011

Last Updated

February 13, 2019

Sponsor

Weill Medical College of Cornell University

Collaborators

University of Toronto, University of Massachusetts, Worcester, University of Pittsburgh

1. Study Identification

Unique Protocol Identification Number

NCT01427608

Brief Title

Sustaining Remission of Psychotic Depression

Acronym

STOP-PD

Official Title

Sustaining Remission of Psychotic Depression

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

November 30, 2017 (Actual)

Study Completion Date

November 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

Collaborators

University of Toronto, University of Massachusetts, Worcester, University of Pittsburgh

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The acute phase of this study will monitor the response to a combination of an atypical antipsychotic medication olanzapine with an antidepressant medication sertraline in the acute treatment of the disorder. It is predicted that this combination will improve symptoms of psychotic depression and be associated metabolic side effects. Factors that moderate tolerability will be monitored. Improvement in symptoms could take between 4 and 12 weeks, followed by a period of 8 weeks during which participants will continue to take the same medications to stabilize the remission from symptoms of psychotic depression. The maintenance phase will be a randomized, double-blind, placebo-controlled study of olanzapine for a period of up to 36 weeks to test whether continuing this combination decreases the risk of relapse and whether discontinuing the combination leads to improvement in metabolic measures. Subjects who complete the acute phase will be asked to consent separately to the randomized maintenance phase.

Detailed Description

The original STOP-PD study established that the combination of olanzapine and sertraline was significantly better than olanzapine alone in achieving remission of psychotic depression. This STOP-PD-II Sustaining Remission study aims to assess the long-term tolerability of taking this combination of medications and their efficacy at preventing a relapse of the symptoms. The acute phase of the study will monitor the efficacy and tolerability of the olanzapine and sertraline combination, including investigation of weight and metabolic variables, age effects on treatment response and tolerability, and the association of genetic polymorphisms to response or relapse. When subjects are stabilized on these medications for a period of 8 weeks they will be invited to participate in the randomized phase of the research: the olanzapine will be placebo-controlled, meaning half of the subjects will continue to take the olanzapine/sertraline combination and half will take a sertraline/placebo combination, for a period of 36 weeks. Symptoms and side effects will be monitored regularly throughout this phase. Randomization will be stratified on a 1:1 basis by age 60 and above.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Psychotic Depression

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

269 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sertraline + Olanzapine

Arm Type

Active Comparator

Arm Description

Randomized to continue with sertraline and olanzapine under double-blind conditions.

Arm Title

Sertraline + Placebo

Arm Type

Placebo Comparator

Arm Description

Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions.

Intervention Type

Drug

Intervention Name(s)

Sertraline + Olanzapine

Other Intervention Name(s)

Zyprexa

Intervention Description

Olanzapine 15mg/day. Adjustment of dose to 5mg/day to a maximum of 20mg/day will be permitted if necessitated by significant side-effects or clinical worsening

Intervention Type

Drug

Intervention Name(s)

Sertraline + Placebo

Other Intervention Name(s)

Placebo

Intervention Description

Taper from current dose of olanzapine to placebo over 4 weeks. Continue placebo for remainder of 36 week study.

Primary Outcome Measure Information:

Title

Number of Subjects at Risk of Relapse During the Randomized Phase.

Description

Time Frame

From entry into randomized phase (baseline) and 36 weeks or earlier relapse

Secondary Outcome Measure Information:

Title

Changes in Metabolic Measures: Weight

Description

Change in weight from entry into randomized phase (baseline) and 36 weeks.

Time Frame

From entry into randomized phase (baseline) and 36 weeks

Title

Changes in Metabolic Measure: Cholesterol

Description

Change in cholesterol from entry into randomized phase (baseline) and 36 weeks.

Time Frame

From entry into randomized phase (baseline) and 36 weeks

Title

Changes in Metabolic Measures: Triglycerides

Description

Change in triglycerides from entry into randomized phase (baseline) and 36 weeks.

Time Frame

From entry into randomized phase (baseline) and 36 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Aged 18-85 years, inclusive Diagnosis: Diagnostic Statistical Manual-IV Trade Revision (DSM IV-TR) non-bipolar major depression with psychotic features established by both clinical interview with research psychiatrist and administration of SCID-IV. Score >2 on Schedule for Affective Disorders (SADS) delusion severity item Score >1 on any of the three conviction items of the Delusion Assessment Scale (DAS) (does not alter belief in response to reality testing) 17-item HAM-D score of >20 Exclusion Criteria: Current or lifetime DSM-IV-TR history of schizophrenia or other psychotic disorders or meeting current criteria for brief psychotic disorder, body dysmorphic disorder or obsessive-compulsive disorder Current or lifetime DSM-IV-TR bipolar affective disorder History of DSM-IV-TR defined alcohol or substance abuse or dependence within the past three months Dementia or clinically significant cognitive impairment prior to index episode of depression, and/or a mean score >3 on 26-item caregiver assessment Type 1 diabetes mellitus (defined as insulin-dependent diabetes mellitus with onset before age 35, and/or diabetes mellitus complicated by prior documented episode of ketoacidosis Acute or unstable medical illness within the past 3 months; current abnormal serum free T4; current abnormally low vitamin B4 or folic acid level; medical conditions and/or medications for which psychotic or depressive symptoms can be a direct manifestation; neurological disease associated with extrapyramidal signs and symptoms; epilepsy, if the person has had one or more grand mal seizures within the past 12 months. The need for treatment with any psychotropic medication other than sertraline, olanzapine or lorazepam; or with an anticonvulsant medication with mood-stabilizing properties. Current pregnancy or plan to become pregnant during the course of the study; breast feeding in women with infants. A documented history of being unable to tolerate olanzapine or sertraline including significant bradycardia (heart rate of <50 bpm), and serum sodium level of 129mmol/L or below. History of non-response of the index episode of psychotic depression to at least a 6-week trial of at least 150mg/day sertraline combined with 15mg/day olanzapine Patients showing ongoing improvement in current episode of psychotic depression with treatment other than sertraline or olanzapine Patients who are in immediate need of electroconvulsive therapy (ECT) (imminent risk of suicide, refusing to eat, catatonic)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

George Alexopoulos, MD

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Alastair Flint, MD

Organizational Affiliation

University of Toronto

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Anthony Rothschild, MD

Organizational Affiliation

University of Massachusetts, Worcester

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ellen Whyte, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

Anthony Rothschild, MD

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01605

Country

United States

Facility Name

George Alexopoulos, MD

City

White Plains

State/Province

New York

ZIP/Postal Code

10605

Country

United States

Facility Name

Ellen Whyte, MD

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

Alastair Flint, MD

City

Toronto

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32101271

Citation

Voineskos AN, Mulsant BH, Dickie EW, Neufeld NH, Rothschild AJ, Whyte EM, Meyers BS, Alexopoulos GS, Hoptman MJ, Lerch JP, Flint AJ. Effects of Antipsychotic Medication on Brain Structure in Patients With Major Depressive Disorder and Psychotic Features: Neuroimaging Findings in the Context of a Randomized Placebo-Controlled Clinical Trial. JAMA Psychiatry. 2020 Jul 1;77(7):674-683. doi: 10.1001/jamapsychiatry.2020.0036.

Results Reference

derived

PubMed Identifier

31429896

Citation

Flint AJ, Meyers BS, Rothschild AJ, Whyte EM, Alexopoulos GS, Rudorfer MV, Marino P, Banerjee S, Pollari CD, Wu Y, Voineskos AN, Mulsant BH; STOP-PD II Study Group. Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission: The STOP-PD II Randomized Clinical Trial. JAMA. 2019 Aug 20;322(7):622-631. doi: 10.1001/jama.2019.10517.

Results Reference

derived

PubMed Identifier

31207561

Citation

Bingham KS, Whyte EM, Mulsant BH, Rothschild AJ, Rudorfer MV, Marino P, Banerjee S, Butters MA, Alexopoulos GS, Meyers BS, Flint AJ; STOP-PD Study Group. Health-related quality of life in remitted psychotic depression✰. J Affect Disord. 2019 Sep 1;256:373-379. doi: 10.1016/j.jad.2019.05.068. Epub 2019 May 28.

Results Reference

derived

PubMed Identifier

23351522

Citation

Flint AJ, Meyers BS, Rothschild AJ, Whyte EM, Mulsant BH, Rudorfer MV, Marino P; STOP-PD II Study Group. Sustaining remission of psychotic depression: rationale, design and methodology of STOP-PD II. BMC Psychiatry. 2013 Jan 25;13:38. doi: 10.1186/1471-244X-13-38.

Results Reference

derived

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Sustaining Remission of Psychotic Depression

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