Contact: Developing New Clinical Management Strategies

Major Depressive Disorder Clinical Trial

Official title:

Developing New Clinical Management Strategies for Antidepressant Treatments

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03812588
• Other study ID #: 7738
• Status: Completed
• Phase: Phase 4
• Start date: January 30, 2019
• Est. completion date: August 1, 2021

Study information

• Verified date: March 2022
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: August 1, 2021
• Est. primary completion date: May 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Inclusion Criteria Method of Ascertainment

1. Men and women aged 18-75 years 1. Clinical interview

2. Diagnosis with Diagnostic and Statistical Manual (DSM) V Major Depressive Disorder (MDD) 2. Clinical interview, Structured Clinical Interview for DSM-V

3. 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

4. Capable of providing informed consent and complying with study procedures 4. Clinical interview

5. Using appropriate contraceptive method if woman of child-bearing age and not currently pregnant 5. Clinical interview

Exclusion Criteria:

1. Current comorbid Axis I DSM V disorder other than Mild Substance Use Disorder, Adjustment Disorder, Anxiety Disorder or Personality Disorder 1. Clinical interview, SCID

2. Diagnosis of Moderate to Severe Substance Use Disorder within the past 12 months 2. Clinical interview, SCID, Urine tox

3. present or past history of psychosis, psychotic disorder, mania, or bipolar disorder

3. Clinical interview, SCID

4. baseline HRSD 24-item score > 28 or HRSD suicide item > 2 or baseline HRSD 17-item score = 25 4. HRSD by trained rater

5. 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

6. Current treatment with psychotherapy, antidepressants, antipsychotics, or mood stabilizers 6. Clinical interview

7. CGI-Severity score of 6 or greater at baseline 7. CGI based on Clinical interview

8. Acute, severe, or unstable medical illness 8. Clinical interview, Physical Exam, Screening Labs

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Escitalopram
Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.
• Placebo
A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	University of Haifa

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline Clinical Global Impressions	Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions correlates well with other standard outcome measures for depression (e.g., HRSD), is sensitive to change in antidepressant trials, and offers clinically understandable anchor points.; 7-point scale: 0 = Not assessed 4 = Moderately ill; 1 = Normal, not at all ill 5 = Markedly ill 2 = Borderline mentally ill 6 = Severely ill 3 = Mildly ill 7 = Among the most extremely ill patients	Up to 8 Weeks
Primary	Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (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	Up to 8 Weeks
Secondary	Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale	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.	Up to 8 Weeks