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Sustaining Remission of Psychotic Depression (STOP-PD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01427608
Recruitment Status : Completed
First Posted : September 1, 2011
Results First Posted : March 5, 2019
Last Update Posted : March 5, 2019
University of Toronto
University of Massachusetts, Worcester
University of Pittsburgh
Information provided by (Responsible Party):
Weill Medical College of Cornell University

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.

Condition or disease Intervention/treatment Phase
Psychotic Depression Drug: Sertraline + Olanzapine Drug: Sertraline + Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 269 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sustaining Remission of Psychotic Depression
Study Start Date : October 2011
Actual Primary Completion Date : November 30, 2017
Actual Study Completion Date : November 30, 2017

Arm Intervention/treatment
Active Comparator: Sertraline + Olanzapine
Randomized to continue with sertraline and olanzapine under double-blind conditions.
Drug: Sertraline + Olanzapine
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
Other Name: Zyprexa

Placebo Comparator: Sertraline + Placebo
Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions.
Drug: Sertraline + Placebo
Taper from current dose of olanzapine to placebo over 4 weeks. Continue placebo for remainder of 36 week study.
Other Name: Placebo

Primary Outcome Measures :
  1. Number of Subjects at Risk of Relapse During the Randomized Phase. [ Time Frame: From entry into randomized phase (baseline) and 36 weeks or earlier relapse ]

    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 :
  1. Changes in Metabolic Measures: Weight [ Time Frame: From entry into randomized phase (baseline) and 36 weeks ]
    Change in weight from entry into randomized phase (baseline) and 36 weeks.

  2. Changes in Metabolic Measure: Cholesterol [ Time Frame: From entry into randomized phase (baseline) and 36 weeks ]
    Change in cholesterol from entry into randomized phase (baseline) and 36 weeks.

  3. Changes in Metabolic Measures: Triglycerides [ Time Frame: From entry into randomized phase (baseline) and 36 weeks ]
    Change in triglycerides from entry into randomized phase (baseline) and 36 weeks.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Aged 18-85 years, inclusive
  2. 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.
  3. Score >2 on Schedule for Affective Disorders (SADS) delusion severity item
  4. Score >1 on any of the three conviction items of the Delusion Assessment Scale (DAS) (does not alter belief in response to reality testing)
  5. 17-item HAM-D score of >20

Exclusion Criteria:

  1. 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
  2. Current or lifetime DSM-IV-TR bipolar affective disorder
  3. History of DSM-IV-TR defined alcohol or substance abuse or dependence within the past three months
  4. Dementia or clinically significant cognitive impairment prior to index episode of depression, and/or a mean score >3 on 26-item caregiver assessment
  5. 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
  6. 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.
  7. The need for treatment with any psychotropic medication other than sertraline, olanzapine or lorazepam; or with an anticonvulsant medication with mood-stabilizing properties.
  8. Current pregnancy or plan to become pregnant during the course of the study; breast feeding in women with infants.
  9. 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.
  10. 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
  11. Patients showing ongoing improvement in current episode of psychotic depression with treatment other than sertraline or olanzapine
  12. Patients who are in immediate need of electroconvulsive therapy (ECT) (imminent risk of suicide, refusing to eat, catatonic)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01427608

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United States, Massachusetts
Anthony Rothschild, MD
Worcester, Massachusetts, United States, 01605
United States, New York
George Alexopoulos, MD
White Plains, New York, United States, 10605
United States, Pennsylvania
Ellen Whyte, MD
Pittsburgh, Pennsylvania, United States, 15213
Alastair Flint, MD
Toronto, Canada
Sponsors and Collaborators
Weill Medical College of Cornell University
University of Toronto
University of Massachusetts, Worcester
University of Pittsburgh
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Principal Investigator: George Alexopoulos, MD Weill Medical College of Cornell University
Principal Investigator: Alastair Flint, MD University of Toronto
Principal Investigator: Anthony Rothschild, MD University of Massachusetts, Worcester
Principal Investigator: Ellen Whyte, MD University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by Weill Medical College of Cornell University:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Weill Medical College of Cornell University Identifier: NCT01427608    
Other Study ID Numbers: STOP-PD-II
First Posted: September 1, 2011    Key Record Dates
Results First Posted: March 5, 2019
Last Update Posted: March 5, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Depressive Disorder
Mental Disorders
Psychotic Disorders
Bipolar Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Bipolar and Related Disorders
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Antidepressive Agents