This will be a single-blind, placebo-run-in trial. Subjects will be informed that they may receive duloxetine or placebo during the course of the trial. All subjects will, in fact, receive placebo for the first two weeks. All subjects will then be placed on 60-90mg per day of duloxetine. Primary outcome assessment will compare pain intensity at 2 weeks (after placebo) to that at 12 weeks (after 10 weeks of duloxetine treatment).

Study Hypothesis:

In subjects who continue to have activity-limiting osteoarthritis pain after treatment with acetaminophen or non-steroidal anti-inflammatory agents, 60-90 mg Duloxetine per day over 10 weeks will provide significant additional pain relief over that achieved with placebo(> 30% reduction after Duloxetine treatment).

Inclusion Criteria:

• Age 50-80
• Physician diagnosis of OA in hip, knee or spine.
• Significant activity limitation due to pain for at least one month on the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) and average pain >5/10 on Brief Pain Inventory despite adequate treatment with acetaminophen or NSAIDs. [This will identify an OA group with significant psychological distress and a desire for treatment.]
• Depression status is not restricted, but will be monitored with PRIME-MD interview and the SCL-20. We anticipate depressive symptoms will be common in this population due to the above requirement for activity limitation.

Exclusion Criteria:

• Cannot read and write English

• Significant cognitive impairment

• History of psychosis or mania

• Current suicidal ideation

  • Current substance abuse or dependence
  • Current use of opioids or any antidepressant medication
  • Use of investigational drug within the past month