Developing New Clinical Management Strategies

NCT02082392 | Completed Phase 4 Results

• 1 other identifier: #6652
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Hamilton Rating Scale for Depression

  scale for depressive symptoms administered by trained rater. The HRSD 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. Although the HRSD list 21 items, the scoring is based on the first 17 items. sum of the scores of the first 17 items (range from 0 to 54): 0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression \>=23 = Very Severe Depression

  Baseline week

Secondary Outcomes (13)

• Hamilton Anxiety Rating Scale (HARS) 14-item Scale

  Baseline week

• CGI Severity and Improvement

  Baseline week

• Treatment Emergent Symptom Scale

  Baseline week

• California Pharmacotherapy Alliance Scale (CALPAS)-Clinician Version

  Baseline week

• Blind Assessment-Clinician Version

  8 weeks

Study Arms (4)

Clinical Frequency Management: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Research Frequency Management: Placebo

PLACEBO COMPARATOR

Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders.

Drug: Placebo

Clinical Frequency Management: Escitalopram

ACTIVE COMPARATOR

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.

Drug: Escitalopram

Research Frequency Management: Escitalopram

ACTIVE COMPARATOR

Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders.

Drug: Escitalopram

Interventions

Escitalopram DRUG

Also known as: Lexapro

Clinical Frequency Management: Escitalopram; Research Frequency Management: Escitalopram

Placebo DRUG

A substance or treatment of no intended therapeutic value in a pill form.

Clinical Frequency Management: Placebo; Research Frequency Management: Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. men and women aged 18-60 years
• \. diagnosis with Diagnostic and Statistical Manual (DSM) IV Major Depressive Disorder (MDD)
• \. 24-item Hamilton Rating Scale for Depression (HRSD) score greater than or equal to 18
• \. capable of providing informed consent and complying with study procedures
• \. using appropriate contraceptive method if woman of child-bearing age

You may not qualify if:

• \. Current comorbid Axis I DSM IV disorder other than Nicotine Dependence, Adjustment Disorder, or Anxiety Disorder
• \. diagnosis of substance abuse or dependence (excluding Nicotine Dependence) within the past 12 months
• \. present or past history of psychosis, psychotic disorder, mania, or bipolar disorder
• \. baseline HRSD score \> 28 or HRSD suicide item \> 2
• \. 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
• \. current treatment with psychotherapy, antidepressants, antipsychotics, or mood stabilizers
• \. CGI-Severity score of 7 at baseline
• \. acute, severe, or unstable medical illness

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bret Rutherford
• Organization: New York State Psychiatric Institute

brr8@cumc.columbia.edu

6467748660

Study Officials

• Bret Rutherford, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: September 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: August 4, 2015
• Last Updated: March 3, 2020
• Results First Posted: July 7, 2017

Record last verified: 2020-02

Locations

US (1)