Contact: Developing New Clinical Management Strategies

Phase 4

Completed

Conditions: Major Depressive Disorder

Interventions: Drug: Placebo
Drug: Escitalopram

Registration Number: NCT03812588

Lead Sponsor: New York State Psychiatric Institute

Brief Summary: The goal of this study is to develop new methods of administering antidepressant medications that will result in improved drug/placebo separation in randomized controlled trials (RCTs) for Major Depressive Disorder (MDD) and enhanced medication response in open clinical treatment. The highly intensive, weekly visit schedule followed in most antidepressant RCTs radically differs from how antidepressant medications are prescribed in standard clinical practice and is believed to be a major reason why the majority of studies submitted to the Food and Drug Administration (FDA) fail to show a significant difference between medication and placebo. Moreover, a "one size fits all" approach to psychopharmacologic management (i.e., weekly visits for all patients) does not take into account differences between patients that may predispose some individuals to respond positively to frequent follow-up visits, while others may respond negatively or not at all. Clinic visits comprise multiple components that may be therapeutic for depression, including activating patients' behavior, exposing them to medical procedures, permitting social interactions with research staff, and providing supportive meetings with clinicians. Two independent meta-analyses have associated more frequent study visits with increased antidepressant and placebo response as well as decreased separation between medication and placebo. Despite the high costs and potential disadvantages of weekly follow-up visits for patients receiving antidepressant medication, this clinical management strategy has not been studied prospectively to date. It is unknown whether weekly follow-up visits are needed to ensure treatment compliance and patient safety in clinical trials and to what degree contacts with clinicians influence medication and placebo response.

Detailed Description: This study utilizes a 2 x 2, double-blind, acute, prospective design randomizing adult

outpatients with MDD to "Research Frequency Management" (RFM, weekly study visits) vs. "Community Frequency Management" (CFM, every 4 weeks study visits) and antidepressant medication vs. placebo. Specifying visit frequency as the independent variable in this study has the distinct advantages of being easily operationalized for research purposes avoiding a priori assumptions about which components of study visits influence antidepressant and placebo response (i.e., behavioral activation vs. doctor-patient relationship vs. medical procedures). Close monitoring of all subjects will be assured by telephone evaluations of individuals randomized to CFM at intervals between monthly visits, and additional study contacts will be scheduled as necessary to maintain patient safety (all extra-protocol contacts will be recorded and included as a variable in outcome analyses). Additionally, subjects will be characterized extensively on clinical, demographic, and psychological measures to pilot the study assessment battery and search for predictor variables influencing the effects of contact frequency on medication and placebo response.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Inclusion Criteria Method of Ascertainment

Men and women aged 18-75 years 1. Clinical interview
Diagnosis with Diagnostic and Statistical Manual (DSM) V Major Depressive Disorder (MDD) 2. Clinical interview, Structured Clinical Interview for DSM-V
24-item Hamilton Rating Scale for Depression (HRSD) score ≥ 16 and ≤ 28; 17-item Hamilton Rating Scale for Depression (HRSD) score < 25 3. HRSD by trained rater
Capable of providing informed consent and complying with study procedures 4. Clinical interview
Using appropriate contraceptive method if woman of child-bearing age and not currently pregnant 5. Clinical interview

Exclusion Criteria

Current comorbid Axis I DSM V disorder other than Mild Substance Use Disorder, Adjustment Disorder, Anxiety Disorder or Personality Disorder 1. Clinical interview, SCID
Diagnosis of Moderate to Severe Substance Use Disorder within the past 12 months 2. Clinical interview, SCID, Urine tox
present or past history of psychosis, psychotic disorder, mania, or bipolar disorder 3. Clinical interview, SCID
baseline HRSD 24-item score > 28 or HRSD suicide item > 2 or baseline HRSD 17-item score ≥ 25 4. HRSD by trained rater
History of allergic or adverse reaction to escitalopram, or non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20mg) during the current episode 5. Clinical interview
Current treatment with psychotherapy, antidepressants, antipsychotics, or mood stabilizers 6. Clinical interview
CGI-Severity score of 6 or greater at baseline 7. CGI based on Clinical interview
Acute, severe, or unstable medical illness 8. Clinical interview, Physical Exam, Screening Labs

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clinical Frequency Management: Placebo	Placebo	Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.
Research Frequency Management: Placebo	Placebo	Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.
Clinical Frequency Management: Escitalopram	Escitalopram	Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.
Research Frequency Management: Escitalopram	Escitalopram	Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.

Primary Outcome Measures

Name	Time	Method
Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)	Up to 8 Weeks	Scale for depressive symptoms administered by trained rater. The Hamilton is the standard measure of depression severity for clinical trials of antidepressants and was chosen as the primary outcome measure over other depression rating scales to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. The scoring is based on the first 24 items of the Hamilton. Sum of the scores of the first 24 items (range from 0 to 74): 0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression \>=23 = Very Severe Depression

Secondary Outcome Measures

Name	Time	Method
Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale	Up to 8 Weeks	Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety is a standard measure of anxiety severity in pharmacotherapy studies that has been shown to have acceptable reliability and validity in studies of depressed patients. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.