Sustaining Remission of Psychotic Depression

NCT ID: NCT01427608

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 269 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2017-11-30

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.

Conditions

Psychotic Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sertraline + Olanzapine

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

Group Type: ACTIVE_COMPARATOR

Sertraline + Olanzapine

Intervention Type: DRUG

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

Sertraline + Placebo

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

Group Type: PLACEBO_COMPARATOR

Sertraline + Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Sertraline + Placebo

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

Intervention Type: DRUG

Other Intervention Names

Zyprexa; Placebo

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Toronto

OTHER

Sponsor Role: collaborator

University of Massachusetts, Worcester

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George Alexopoulos, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Alastair Flint, MD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Anthony Rothschild, MD

Role: PRINCIPAL_INVESTIGATOR

University of Massachusetts, Worcester

Ellen Whyte, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Anthony Rothschild, MD

Worcester, Massachusetts, United States

George Alexopoulos, MD

White Plains, New York, United States

Ellen Whyte, MD

Pittsburgh, Pennsylvania, United States

Alastair Flint, MD

Toronto, , Canada

Countries

United States; Canada

References

Bingham KS, Calarco N, Dickie EW, Alexopoulos GS, Butters MA, Meyers BS, Marino P, Neufeld NH, Rothschild AJ, Whyte EM, Mulsant BH, Flint AJ, Voineskos AN. The relationship of white matter microstructure with psychomotor disturbance and relapse in remitted psychotic depression. J Affect Disord. 2023 Aug 1;334:317-324. doi: 10.1016/j.jad.2023.04.136. Epub 2023 May 4.

Reference Type: DERIVED

PMID: 37149056 (View on PubMed)

Flint AJ, Bingham KS, Alexopoulos GS, Marino P, Mulsant BH, Neufeld NH, Rothschild AJ, Voineskos AN, Whyte EM, Meyers BS; STOP-PD II Study Group. Predictors of relapse of psychotic depression: Findings from the STOP-PD II randomized clinical trial. J Psychiatr Res. 2023 Jan;157:285-290. doi: 10.1016/j.jpsychires.2022.12.011. Epub 2022 Dec 12.

Reference Type: DERIVED

PMID: 36535116 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32101271 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31429896 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31207561 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23351522 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STOP-PD-II

Identifier Type: -

Identifier Source: org_study_id