A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center)
A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center)
This study is comprised of three separate pharmacogenetic trials grouped into a single
 protocol due to similarities in the intervention, the hypotheses, and the trial design. The
 three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial.
 Participants can enroll in only one of the three trials.

 Acute Pain Trial: A prospective, multicenter, two arm randomized pragmatic trial.
 Participants meeting eligibility criteria will be randomly assigned to either immediate
 pharmacogenetic testing and genotype-guided post-surgical opioid therapy (Intervention arm)
 or standard care and pharmacogenetic testing after 6 months (Control arm). The investigators
 will test the hypothesis that pharmacogenetic testing and genotype guided pain management
 therapy improves pain control after surgery in participants who's body processes some pain
 medicines slower than normal.

 Chronic Pain Trial: A prospective, multicenter, two arm randomized pragmatic trial.
 Participants meeting eligibility criteria will be randomly assigned to either immediate
 pharmacogenetic testing and genotype-guided opioid therapy (Intervention arm) or standard
 care with 6-month delayed pharmacogenetic testing (Control arm). The investigators will test
 the hypothesis that pharmacogenetic testing and genotype guided pain therapy improves pain
 control after surgery in participants who's body processes some pain medicines slower than
 normal.

 Depression: A prospective, multicenter, two arm randomized pragmatic trial. Participants
 meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic
 testing and genotype-guided anti-depressant therapy (Intervention arm) or standard care with
 6-month delayed pharmacogenetic testing (Control arm). The investigators will test the
 hypothesis that pharmacogenetic testing and genotype-guided anti-depressant therapy will
 reduce depression symptoms in participants who's body processes some anti-depressants faster
 or slower than normal.
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:

 Acute Pain Trial: Determine if a genotype-guided approach to acute post-surgical pain therapy
 leads to improved pain control compared to usual care, as defined by a decrease in the SIA
 score. Secondarily, The investigators will evaluate whether this approach leads to reduced
 use of DEA Schedule II opioids and reduced pain intensity.

 Chronic Pain Trial: 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.

 Depression Trial: 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:

 Acute Pain

 -  Age ≥ 8 years (pediatrics), as this is the minimum age at which proposed outcome
 measures (PROMIS) are validated without parent proxy

 -  English speaking or Spanish speaking

 -  Elective/planned surgery patients with an upcoming pre-surgery visit

 -  Elective/planned surgery types with pain management, which may include orthopedic
 surgeries (e.g. arthroplasty, spine, etc.), open abdominal surgery, or cardiothoracic
 surgery and others

 Chronic Pain

 -  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 relevant specialty clinics

 -  Under the care of a physician for pain for at least 3 months and currently or being
 considered to be treated with tramadol, hydrocodone, or codeine to improve pain
 management

 -  Pain diagnosis

 -  Underlying conditions with chronic pain if a pain diagnosis does not exist (not a
 comprehensive list): arthritis, neuropathy, fibromyalgia, headache.

 -  Have a current or planned pain prescription: tramadol, hydrocodone, or codeine

 Depression

 -  Age ≥ 8 years, as this is the minimum age at which proposed outcome measures (PROMIS)
 are validated without parent proxy

 -  English speaking or Spanish speaking

 -  Patients seen at primary care clinics (such as, but not limited to, Internal Medicine,
 Family Medicine, or Pediatrics) or in psychiatry clinics

 -  Diagnosis of depression, defined as problem list entry or ICD-10 diagnosis code with
 at least 3 months of symptoms

 -  Anticipate need for revised or new SSRI therapy for depression

 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)

 -  Plan to move out of the area within 6 months of enrollment

 -  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

 Acute Pain

 -  Adults with a similar, previous surgery in whom pain control is well-defined and a
 genotype-guided approach would not likely be followed

 -  Undergoing a laparoscopic surgery

 -  Receiving chronic opioid therapy, defined as use of opioids on most days for >3 months

 Chronic Pain

 ● Undergoing treatment for an active cancer diagnosis

 Depression

 -  Have active psychosis or diagnosed psychotic disorders (schizophrenia, schizoaffective
 disorder, delusional disorder, psychotic depression, substance induced psychosis,
 schizophreniform disorder)

 -  ICD10: F06.2, F20.x, F25.x, F22, F20.81

 -  Or a problem list entry indicating the diagnosis of one of these disorders

 -  Have dementia or other neurocognitive disorders (due to any cause, such as Alzheimer's
 disease, vascular/subcortical, lewy body, frontotemporal lobar degeneration)

 -  ICD10: F01, F03.x, G31.83, G30.x, G31.09

 -  Or a problem list entry indicating the diagnosis of one of these disorders

 -  Have cognitive developmental delay and/or cognitive disability, including autism
 spectrum disorders (Note: this list does not include ADHD)

 -  ICD10: F80.x, F81.x, F82.x, F83.x, F84.x, F85.x, F88.x, F89.x

 -  Or a problem list entry indicating the diagnosis of one of these disorders

 -  Have seizures, or who are on a neuroleptic medication

 -  ICD10: G40.x, G41.x

 -  Medications: aripiprazole, asenapine, cariprazine, clozapine, lurasidone,
 olanzapine, quetiapine, risperidone

 -  Or a problem list entry indicating the diagnosis of one of these disorders

 -  Have bipolar disorder

 -  IDC10: F31.x

 -  Or a problem list entry indicating the diagnosis of one of these disorders

 -  Depression secondary to substance abuse disorder or general medical condition