RAPID: Reducing Pain; Preventing Depression

In this Sequential Multiple Assignment Randomized (SMART) Trial, the investigators care comparing Cognitive Behavioral Therapy for Pain (CBT-P) with EXERCISE (knee-specific Physical Therapy) delivered individually and sequentially. A subset of participants will receive enhanced care as usual in which their primary care physicians will receive information about pharmacological management of knee osteoarthritis. The active phase of the study may be up to 16 weeks, and the follow-up period lasts 12 months. Stage 1, Specific Aim 1: To test if Cognitive Behavioral Therapy for Pain (CBT-P) results in more improvement in pain and disability than those receiving knee-specific Physical Therapy (EXERCISE). Stage 1, Hypothesis 1: At week 8, subjects randomized to CBT-P will have more improvement in pain and disability than those randomized to EXERCISE. Stage 2, Specific Aim 2: For non-responders to Stage 1, to explore which sequence of interventions leads to greater improvement in pain and disability. Stage 2, Hypothesis 2: Compared to the other sequenced interventions (see Figure), subjects randomized to CBT-P and then EXERCISE will have the most improvement in pain and disability. Follow-up, Specific Aim 3: To explore if improvement in pain and disability is associated with incident major depressive episode (MDE) over 12 months. Follow-up, Hypothesis 3: More pain and disability improvement will be associated with lower rates of incident (MDE) over 12 months. Exploratory AIM 1: To compare "legacy" assessments of functioning and psychological health with Computer Adaptive Testing (CAT) assessments of these domains for level of agreement. Exploratory AIM 2: To assess candidate genetic polymorphisms, peripheral mRNA biosignatures, and candidate cytokine and growth factor levels using both multiplex assays and individual ELISAs. The investigators are exploring if these biomarkers are associated with pain improvement and risk for developing MDE.