Sustaining Remission of Psychotic Depression

Psychotic Depression Clinical Trial

— STOP-PD  

Official title:

Sustaining Remission of Psychotic Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01427608
• Other study ID #: STOP-PD-II
• Status: Completed
• Phase: Phase 4
• Start date: October 2011
• Est. completion date: November 30, 2017

Study information

• Verified date: February 2019
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 269
• Est. completion date: November 30, 2017
• Est. primary completion date: November 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Mental Disorders
• Psychotic Depression
• Psychotic Disorders

Intervention

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

Locations

Country	Name	City	State
Canada	Alastair Flint, MD	Toronto
United States	Ellen Whyte, MD	Pittsburgh	Pennsylvania
United States	George Alexopoulos, MD	White Plains	New York
United States	Anthony Rothschild, MD	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	University of Massachusetts, Worcester, University of Pittsburgh, University of Toronto

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes in Metabolic Measures: Weight	Change in weight from entry into randomized phase (baseline) and 36 weeks.	From entry into randomized phase (baseline) and 36 weeks
Secondary	Changes in Metabolic Measure: Cholesterol	Change in cholesterol from entry into randomized phase (baseline) and 36 weeks.	From entry into randomized phase (baseline) and 36 weeks
Secondary	Changes in Metabolic Measures: Triglycerides	Change in triglycerides from entry into randomized phase (baseline) and 36 weeks.	From entry into randomized phase (baseline) and 36 weeks