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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
269
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
Taper from current dose of olanzapine to placebo over 4 weeks. Continue placebo for remainder of 36 week study.
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
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.
Time frame: From entry into randomized phase (baseline) and 36 weeks or earlier relapse
Changes in Metabolic Measures: Weight
Change in weight from entry into randomized phase (baseline) and 36 weeks.
Time frame: From entry into randomized phase (baseline) and 36 weeks
Changes in Metabolic Measure: Cholesterol
Change in cholesterol from entry into randomized phase (baseline) and 36 weeks.
Time frame: From entry into randomized phase (baseline) and 36 weeks
Changes in Metabolic Measures: Triglycerides
Change in triglycerides from entry into randomized phase (baseline) and 36 weeks.
Time frame: From entry into randomized phase (baseline) and 36 weeks
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