A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Chronic Pain Trial)

Pain and depression are conditions that impact substantial proportions of the US population. Finding safe and effective drug therapies for both conditions is challenging. In the case of treatment for acute and chronic pain, the challenge is finding effective therapy while minimizing adverse effects or opioid addiction (and the ensuing consequences). For depression, there are few clinically relevant predictors of successful treatment leading to multiple trials of inadequate therapy for some patients. Both opioid and antidepressant prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC).

This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic setting.

The rationale for examining a genotype-guided approach to acute and chronic pain management is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and hydrocodone and data from a pilot study supporting improved pain control in intermediate and poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline. Similarly, the rationale for examining a genotype-guided approach to depression medication therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19 oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials support the hypothesis of improved depression symptom control in a genotype-guided arm.

Study objectives:

Determine if a genotype-guided approach to pain therapy in participants with at least 3 months of chronic pain leads to improved pain control compared to usual care.

Inclusion criteria

Chronic Pain Trial

• Age ≥ 18 years
• English speaking or Spanish speaking
• Seen at primary care clinics (such as, but not limited to, Internal Medicine, Family Medicine or Pediatrics) or patients seen in pain-relevant specialty clinics
• History of pain for at least the last 3 months
• Currently treated or being considered for treatment with tramadol, hydrocodone, or codeine to improve pain management

Exclusion criteria

Trial-wide:

• Life expectancy less than 12 months
• Are too cognitively impaired to provide informed consent and/or complete study protocol
• Are institutionalized or too ill to participate (i.e. mental or nursing home facility or incarcerated)
• Have a history of allogeneic stem cell transplant or liver transplant
• People with prior clinical pharmacogenetic test results for genes relevant for the study in which they will enroll (CYP2D6 for the pain studies and CYP2D6 or CYP2C19 for depression) or already enrolled in an ADOPT PGx trial

Chronic Pain

• Plan to move out of the area within 6 months of enrollment
• Undergoing treatment for an active cancer diagnosis
• Currently taking daily opioids other than tramadol, codeine or hydrocodone