Duloxetine Treatment of Major Depression and Chronic Low Back Pain For Older Adults

Study Overview
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Brief Summary
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The following primary hypotheses will be tested: During Step 1: Major Depressive Disorder (MDD) or Chronic Low Back Pain (CLBP) in < 40% of the initial 60 subjects treated with duloxetine (DUL) + Clinical Management(CM) during the first 8 weeks will respond (response is defined as a Montgomery Asberg Depression Rating Scale (MADRS) score </=9 and at least a 30% improvement in back pain as measured with the 20-point numeric rating scale. During Step 2: More DUL+Problem Solving Therapy for Depression and Pain (PST-DP) than DUL+CM treated subjects will achieve response during the second 8 weeks, defined as a MADRS score </=9 and at least a 30% improvement in back pain as measured with the 2-point numeric rating scale. Improvement in depression scores will be correlated with improvement in CLBP scores. The exploratory hypotheses to be tested are that: During Step 2: Compared to subjects treated with DUL+CM, subjects treated with DUL+PST-DP will have improved outcomes in: 1) disability, 2) sleep, 2) functioning/quality of life, 3) caregiver burden/depression, and 5) analgesic use.

Detailed Description
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This is a two-part study. Step 1 is an 8-week long open-label trial of duloxetine (DUL) + clinical management (CM), titrated up to 90 mg/day, for older adults with comorbid major depressive disorder (MDD) and chronic low back pain (CLBP). At week 8, if subjects have not responded, the dose of duloxetine is increased to 120 mg/day. Duloxetine will be increased and continued at 120 mg/day (or highest tolerated dose) for both randomized study groups (during step 2) to assure medication parity. Step two starts at week 9 and includes those subjects whose MDD and/or CLBP has not met criteria for response during Step 1. At week 9 subjects will be randomized to receive treatment with either: 1) DUL 120 mg/day (or the highest tolerated dose)+ Problem Solving for Depression and Pain (PST-DP) or 2) DUL 120 mg/day (or highest tolerated dose) + CM. Step 2 will be delivered over the course of 8-10 sessions. NOTE ADDED 1/5/16: THIS WAS TREATMENT DEVELOPMENT WORK CONDUCTED AS PART OF A CAREER DEVELOPMENT AWARD. ONLY THE FIRST OPEN-LABEL PART OF THE STUDY WAS COMPLETED, AND THESE RESULTS HAVE BEEN PUBLISHED AND WILL BE REPORTED HERE ON CLINICALTRIALS.GOV

Official Title
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Optimizing Outcomes in Older Adults With Low Back Pain and Depression

Conditions
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Major Depressive Disorder, Back Pain, Aged

Intervention / Treatment
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* Drug: Duloxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >/= 60 Current episode of MDD per SCID DSM-IV criteria Must score >/= 16 on the CES-D assessment Serum sodium >/=130 mEq/ml CLBP of at least moderate severity for more days than not for >/= 3 months MADRS score >/= 15 Sufficiently medically stable to be able to participate in a depression treatment protocol Willingness and ability to speak English Access to translators is limited. It would be unsafe to treat an older adult who does not speak English with an antidepressant and not be able to effectively communicate with them about their progress and any side effects. We provide a 24/7 on-call service for all subjects enrolled in this study. The on-call clinicians and physicians are not bilingual, and if a problem arose, it may be impossible to effectively interpret and manage the emergent situation. Finally, many of the assessments used in the study are self-reports. At the present time, we do not have the ability to translate these instruments into other languages. If the subject cannot read and understand English, this would interfere with their ability to complete the self-report assessments Willingness to discontinue other antidepressants and anxiolytics, except for lorazepam up to 2 mg/day Mini Mental State Exam > 20 Willingness to provide informed consent Corrected visual ability that enables reading of newspaper headlines and hearing capacity that is adequate to respond to a raised conversational voice. Exclusion Criteria: Meet DSM-IV criteria for dementia History of bipolar, schizophrenia, schizoaffective, or other psychotic disorder Alcohol or other drug abuse (including abuse of prescription medications) within the past 6 months History of treatment non-adherence in other protocols run by the Mid-Life or Late-Life Centers Acute pain superimposed on chronic pain. For example, subjects who report red flags which suggest a herniated disk, vertebral fracture, infection, cauda equina syndrome, or other medical emergency will be excluded Wheelchair bound History of documented non-response to duloxetine Concurrent use of thioridazine Active suicidal ideation with plan Uncontrolled narrow angle glaucoma

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Duloxetine + clinical management NOTE -- THIS WORK WAS CONDUCTED AS PART OF A CAREER DEVELOPMENT AWARD. THE CLINICALTRIALS.GOV DESCRIPTION OF THE STUDY WAS UPDATED 1/5/16 TO UPDATE THE OPEN LABEL NATURE OF THIS WORK. THIS IS WHAT IS REPORTED HERE AND HAS BEEN PEER REVIEWED AND PUBLISHED. | Drug: Duloxetine<br>* Duloxetine up to 120 mg/day + Clinical Management<br>* Other names: Duloxetine = Cymbalta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery Asberg Depression Rating Scale(MADRS) Score From Baseline and 12 Weeks | The MADRS is a rating of depression severity with theoretical scale range 0-60, with lower values representing better outcome Larger reduction between MADRS from baseline to 12 weeks would represent better outcome | baseline and 12 weeks | 
| Change in McGill Pain Questionaire, Short Form, Score From Baseline and 12 Weeks | The McGill Pain Questionaire, short form consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. The McGill Pain Questionaire score ranged from 0 (none) to 45 (severe). A larger reduction of the score from baseline to 12 weeks would represent a better outcome | Baseline and 12 weeks |