Sustaining Remission of Psychotic Depression (STOP-PD)

Study Description

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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: Olanzapine; Drug: 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated 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
Estimated Primary Completion Date :	July 2018
Estimated Study Completion Date :	July 2018

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Olanzapine; Olanzapine 15mg/day plus sertraline 150mg/day. Fluctuations in dosing are allowed up to a maximum of olanzapine 20mg/day, sertraline 200mg/day.	Drug: 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: Placebo; Placebo will be used to taper the olanzapine over a period of four weeks and then substitute for the olanzapine for the remainder of the 36 week study.	Drug: Placebo; Taper from current dose of olanzapine to placebo over 4 weeks. Continue placebo for remainder of 36 week study.

Outcome Measures

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Primary Outcome Measures :

1. Risk of relapse during the randomized phase. [ Time Frame: From entry into randomized phase until 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 (HAM-D)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 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 [ Time Frame: From entry into randomized phase until up to 36 weeks later ]
   Weight and clinical laboratory analyses of cholesterol and triglycerides

Other Outcome Measures:

1. Age differences in treatment response Under60/60 or older [ Time Frame: 36 weeks ]
   Metabolic changes and symptom response will be compared for 'old' versus 'young'

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

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Locations

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
Canada
Alastair Flint, MD
Toronto, Canada

Sponsors and Collaborators

Weill Medical College of Cornell University

University of Toronto

University of Massachusetts, Worcester

University of Pittsburgh

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT01427608 History of Changes
Other Study ID Numbers:	STOP-PD-II
First Posted:	September 1, 2011
Last Update Posted:	May 1, 2018
Last Verified:	April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:

Depression; 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; Olanzapine; Antiemetics; 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