A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Depression 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 genotype-guided dosing or selection of antidepressants among participants with at least 3 months of depressive symptoms who require new or revised antidepressant therapy leads to improved control of depression, compared to usual care.

Inclusion criteria

Depression Trial

• Age ≥ 8 years
• English speaking or Spanish speaking
• Patients followed at psychiatry clinics or primary care clinics at an enrolling site (such as, but not limited to, Internal Medicine, Family Medicine, or Pediatrics)
• Documentation of depression and/or provider report of depression
• Evidence of depressive symptoms for at least 3 months based on patient interview or documentation in electronic health records
• Recent initiation of SSRI therapy, recent revised SSRI therapy, or anticipated need for revised or new SSRI therapy per health care provider

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

Depression Trial

• Plan to move out of the area within 6 months of enrollment
• Have active psychosis or diagnosed psychotic disorders (schizophrenia, schizoaffective disorder, delusional disorder, psychotic depression, substance induced psychosis, schizophreniform disorder)
• Have dementia or other neurocognitive disorders due to any cause, such as Alzheimer's disease, vascular/subcortical, lewy body disease, frontotemporal lobar degeneration
• Have cognitive developmental delay and/or cognitive disability, including autism spectrum disorders (Note: ADHD is not an exclusion criteria)
• Has a seizure disorder
• Have bipolar disorder