Advancing Personalized Antidepressant Treatment Using PET/MRI
Condition: Depression
MeSH terms: Depression
Intervention: Escitalopram; Placebo
Intervention description: Participants randomized to the escitalopram group will be given the medication for 8 weeks, after which they will be given the option to continue for 4 more weeks if they are close to remission. This additional 4-week treatment option is something offered to participants outside the clinical trial, and therefore was not treated as part of the main study.; To reduce the burden of the patients on placebo, the placebo trial will have a target of 8 weeks. To provide an opportunity for placebo non-responders to receive active drug and to aid in recruitment, we will provide 8-12 weeks of SSRI treatment to placebo non-responders. This treatment option is something offered to participants outside the clinical trial, and therefore was not treated as part of the main study.
Intervention MeSH terms: Escitalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Despite current medications, morbidity and mortality of Major Depressive Disorder (MDD)
      remain high. According to the World Health Organization, MDD affects 121 million people
      worldwide, and is projected to be the second leading cause of global disability by 2020.
      Monotherapy with selective serotonin reuptake inhibitors (SSRIs) is the most widely used
      treatment for MDD. However, on average, SSRIs require six weeks for onset of action, and
      two-thirds of those on SSRIs fail to achieve remission. Compounding this problem, patients
      with residual symptoms are significantly more likely to discontinue treatment or relapse, be
      hospitalized for medical and psychiatric conditions, or die of suicide and other causes.
      Although eliminating ineffective treatment trials would significantly reduce patient
      suffering and healthcare costs,clinicians currently do not have the tools to objectively
      select treatment based on an individual's likelihood of remission. Therefore, there is an
      urgent need to identify markers predictive of an individual's SSRI treatment outcome.
      Developing this personalized treatment requires increased understanding of the relationship
      between pretreatment neurobiology, SSRI-induced biological changes, and the corresponding
      symptom improvements.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age range: over 18 years old

          2. Capacity to consent

          3. Diagnosis of MDD and suffering from a major depressive episode

          4. Score of at least 22 on the MADRS

        Exclusion Criteria:

          1. Significant active physical illness, particularly those that may affect the brain

          2. Need for use of medication during the study that will interact with the study
             medication. Need to start medication that will affect study results (anti epileptics,
             antidepressants, beta blockers, medications with serotonergic or GABAergic modes of
             action)

          3. Patients considered at significant risk for suicide

          4. Patient is unlikely to be able to tolerate medication washout or the ~3 week interval
             (5 for fluoxetine) following washout (drug free period). Medication washouts will be
             supervised by a study physician.

          5. For females: Pregnancy, currently lactating; planning to conceive during the course of
             study participation, or abortion in the past two months.

          6. Coumadin treatment within 10 days of PET scanning

          7. Any MRI contraindications, including metal implants, pacemaker, metal prostheses,
             orthodontic appliances, or presence of shrapnel that are contraindicated for MRI.

          8. Bipolar Disorder

          9. Current psychosis

         10. High potential for excessive drug/alcohol use during the treatment period (excluding
             nicotine or cannabis)

         11. Currently taking effective antidepressant

         12. Currently taking an effective antidepressant

         13. Prior intolerance escitalopram (ESC) for ≥ 4 weeks taking ≥ ⅔ Physician's Desk
             Reference (PDR) maximal dose

         14. Significant neurological deficits

         15. Electroconvulsive Therapy (ECT) within the past 6 months