Promoting Enhanced Pharmacotherapy Choice Through Immunomarkers Evaluation in Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Intervention: Escitalopram; Bupropion
Intervention description: Escitalopram will be started at 5 mg/day during the first week of treatment. The dose will then be increased to 10mg/day, and can be increased to 20 mg/day. Dose can be decreased to 5 mg by clinician discretion such as to increase tolerability or better manage side-effects. 5 mg will be the lowest dose allowed in the study.; Bupropion-XL will be started at 150 mg/day and increased to 300 mg/day after one week. This dose can be increased to 450 mg/day (divided in 2 doses) at Week 2 or later. Clinicians may opt to titrate bupropion-XL in a slower fashion in cases that might increase tolerability or better manage side-effects. 150 mg will be the lowest dose allowed in the study.
Intervention MeSH terms: Bupropion; Escitalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be assigned to one of two groups based on their CRP levels:
CRP less than 1
CRP greater than or equal to 1
Participants within both groups will then be randomized to one of 2 groups, which is stratified by a CRP group:
CRP consistent antidepressant selection (medication will be prescribed based on CRP level)
CRP inconsistent antidepressant selection (medication will be prescribed in contradiction to CRP level)
Masking: None (Open Label)
Masking description: Participant, care provider, investigator, and outcomes assessor will only be blinded to the participant's CRP levels and group assignment. However, the study is open label, meaning the participant, care provider, investigator, and outcomes assessor will know what medication the participant is taking.
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: depression; mental health; mood disorders; major depressive episode; major depressive disorder; antidepressants; escitalopram; bupropion; depression treatment

Summary:

      PRECISE-D is a single site, randomized, open label 8-week clinical trial that will enroll 70
      participants to evaluate if the level of inflammation in our body can predict how we will
      respond to antidepressants. C-reactive protein (CRP) is a substance in the body that is
      associated with inflammation. Previous research has suggested that people with high CRP
      (i.e., high inflammation levels) tend to have greater improvement of depressive symptoms with
      an antidepressant called bupropion, while individuals with low CRP (i.e., low inflammation
      levels) appear to have more benefit from selective serotonin reuptake inhibitors
      antidepressants (SSRI), such as escitalopram. However, it is not completely clear if CRP can
      predict your response to these two antidepressants.

      Participants will undergo a screening visit that includes a physical exam, overall health
      evaluation, assessment of mental health history, and a toxicology and pregnancy test. Once
      screening is complete, participants will be randomized to one of two groups that will
      determine whether their CRP levels will be used to select which antidepressant they will
      receive. Participants will then complete 4 follow up visits at weeks 2, 4, 6, and 8. A
      follow-up phone call from the study team will occur at week 12.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women and men ages 18-65

          -  Current diagnosis of Major Depressive Disorder

          -  Able to read, speak, and understand English

        Exclusion Criteria:

          -  Antidepressant use within the last 8 weeks

          -  Active infection or uncontrolled autoimmune disease

          -  Currently on oral corticosteroids or active immune suppressive therapy (methotrexate,
             cyclosporine, anti-cytokines medications, etc).

          -  Current diagnosis of uncontrolled HIV, hepatitis C or significant immunodeficiency

          -  Alcohol or substance use disorder

          -  Positive urine drug test for illicit substances or substances used out of the context
             of prescription

          -  Cognitively unable to give informed consent

          -  Pregnant or breastfeeding women, women of childbearing potential who are not using an
             accepted means of birth control, or women with a positive urine pregnancy test

          -  History of seizure disorder

          -  Previous significant adverse reaction to escitalopram or bupropion

          -  History of non-response to adequate doses of escitalopram or bupropion XL

          -  Current use of concomitant psychotropic agents (anticonvulsants, benzodiazepines,
             hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone,
             melatonin, folate, l-methylfolate, s-adenosyl methionine, lithium) not on the same
             dose for at least four weeks prior to study entry or who do not agree to continue at
             the same dose during the acute phase of the study.

          -  Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder or other
             psychotic disorder

          -  Current anorexia nervosa or bulimia nervosa

          -  Suicidal ideation of the degree that, in the opinion of the evaluating clinician,
             participation in the study would place them at significantly increased risk of suicide

          -  Unstable medical issues of such degree that, in the opinion of the evaluating
             clinician, participation in the study would place them at significant risk of a
             serious adverse event