Clinical trial NCT03812588: Contact: Developing New Clinical Management Strategies
Official title: Developing New Clinical Management Strategies for Antidepressant Treatments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: University of Haifa
First posted: 2019-01-23
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)
timeFrame: Up to 8 Weeks
Secondary outcomes:
measure: Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale
timeFrame: Up to 8 Weeks
Other outcomes:
measure: Change From Baseline Clinical Global Impressions
timeFrame: Up to 8 Weeks
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Bret Rutherford, MD
role: PRINCIPAL_INVESTIGATOR
References: