Sustaining Remission of Psychotic Depression

NCT01427608 | Completed Phase 4 Results DMC

• 1 other identifier: STOP-PD-II
• Study Type: interventional
• Target: 269
• Locations: 2 countries
• Sites: 4

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.

Conditions

Psychotic Depression

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (3)

• Changes in Metabolic Measures: Weight

  From entry into randomized phase (baseline) and 36 weeks

• Changes in Metabolic Measure: Cholesterol

  From entry into randomized phase (baseline) and 36 weeks

• Changes in Metabolic Measures: Triglycerides

  From entry into randomized phase (baseline) and 36 weeks

Study Arms (2)

Sertraline + Olanzapine

ACTIVE COMPARATOR

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

Drug: Sertraline + Olanzapine

Sertraline + Placebo

PLACEBO COMPARATOR

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

Drug: Sertraline + Placebo

Interventions

Sertraline + Olanzapine 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

Also known as: Zyprexa

Sertraline + Olanzapine

Sertraline + Placebo DRUG

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

Also known as: Placebo

Sertraline + Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• item HAM-D score of \>20

You may not qualify if:

• 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)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• University of Toronto: collaborator
• University of Massachusetts, Worcester: collaborator
• University of Pittsburgh: collaborator

Study Sites (4)

Anthony Rothschild, MD

Worcester, Massachusetts, 01605, United States

Location

George Alexopoulos, MD

White Plains, New York, 10605, United States

Location

Ellen Whyte, MD

Pittsburgh, Pennsylvania, 15213, United States

Location

Alastair Flint, MD

Toronto, Canada

Location

Related Publications (7)

• Neufeld NH, Oliver LD, Mulsant BH, Alexopoulos GS, Hoptman MJ, Tani H, Marino P, Meyers BS, Rothschild AJ, Whyte EM, Bingham KS, Flint AJ, Voineskos AN. Effects of antipsychotic medication on functional connectivity in major depressive disorder with psychotic features. Mol Psychiatry. 2023 Aug;28(8):3305-3313. doi: 10.1038/s41380-023-02118-8. Epub 2023 May 31.

  PMID: 37258617 DERIVED

• 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.

  PMID: 37149056 DERIVED

• 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.

  PMID: 36535116 DERIVED

• 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.

  PMID: 32101271 DERIVED

• 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.

  PMID: 31429896 DERIVED

• 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.

  PMID: 31207561 DERIVED

• 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.

  PMID: 23351522 DERIVED

MeSH Terms

Interventions

Sertraline; Olanzapine

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. George S. Alexopoulos
• Organization: Weill Cornell Medicine

gsalexop@med.cornell.edu

(914) 997-5767

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2011
• First Posted: September 1, 2011
• Study Start: October 1, 2011
• Primary Completion: November 30, 2017
• Study Completion: November 30, 2017
• Last Updated: March 5, 2019
• Results First Posted: March 5, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (3)