Milnacipran for Treatment of Pain in Older Adults With Rheumatoid Arthritis

Inclusion Criteria: Diagnosis. RA subjects will be evaluated by Dr. Ranganath (Board Certified Rheumatologist) using revised criteria established by the ACR (Arnett et al., 1988). This requires at least four of the following seven criteria: 1) morning joint stiffness; 2) arthritis in 3 or more joint areas; 3) arthritis of hand joints; 4) symmetric arthritis; 5) rheumatoid nodules; 6) presence of serum rheumatoid factor and 7) changes on posteroanterior hand and wrist radiographs. In addition, criteria 1-4 must be present for at least four weeks. Individuals diagnosed with juvenile RA will be excluded.

Inclusion Criteria: Medication Use for RA patients. RA subjects taking disease modifying anti-rheumatic drugs (DMARDs) must be on a stable regime for one month before study and stable throughout study. RA subjects using DMARDs will be categorized as follows: 1) no DMARDs; 2) DMARD monotherapy with sulfasalazine, hydroxychloroquine, minocycline, or azothioprine, 3) DMARD monotherapy with methotrexate or leflunamide, 4) biologic therapy with or without concomitant DMARDs.

Exclusion Criteria: Medical conditions. Subjects will not be eligible for the study based on the following criteria: (1) presence of acute or uncontrolled co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke, uncontrolled HTN) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders; (2) presence of co-morbid inflammatory disorders such as Crohn's disease and ulcerative colitis and other autoimmune disorders; (3) presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or put the study participant at undue risk; (4) presence of chronic infections (e.g. positive PPD test) due to contraindication of TNF antagonist use in these individuals and also because chronic infection can produce elevations in proinflammatory cytokines; (5) presence of an acute infectious illness in the two weeks prior to an experimental session; (6) pregnancy or breast-feeding because of the effects on neuroendocrine systems and sleep; (7) in women, the presence of vasomotor symptoms due to the effects of such symptoms on measures of sleep; (8) use of hormone containing medications including steroids; (9) current and/or regular use of NSAID medications.

Exclusion Criteria: Psychiatric Disorders. RA subjects with a current or lifetime history of a major Depressive Disorder or other DSM-IV psychiatric disorder (e.g. substance dependence) will be excluded due to the known effects of major depression on pain. Although depressive symptoms can occur in as many as 40% of RA patients, the prevalence of syndromal major depressive disorder is considerably less, and we do not anticipate that exclusion of current or lifetime history of major depressive disorder will substantially alter subject flow. More than 75% of a selected sample of RA subjects at UCLA affiliated clinics does not have a history of co-morbid psychiatric disorder.

Exclusion Criteria: Medication use. Subjects who have used the following medications in the past two months will be excluded from the study: (1) previous use of Nitrogen Mustard, Cyclosporin, Cytotoxin, or Cyclophosphamide; (2) regular use of analgesics such as opioids, (3) regular use of prednisone >10mg of prednisone, (4) psychotropic medications, including selective serotinergic reuptake inhibitors, antidepressants, anxiolytics, hypnotics, sedatives and barbiturates. We will also exclude current smokers because of the known effects of tobacco use on proinflammatory cytokine levels. (Helen, I would suggest to remove this sentence. It is clear from studies that patients are higher risk for susceptibility and increased disease activity with smoking. It may decrease our enrollment.)