Developing New Clinical Management Strategies

New York State Psychiatric Institute

Status and phase: Completed; Phase 4

Conditions: Major Depressive Disorder

Treatments: Drug: Escitalopram; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02082392

#6652

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1. men and women aged 18-60 years
• 2. diagnosis with Diagnostic and Statistical Manual (DSM) IV Major Depressive Disorder (MDD)
• 3. 24-item Hamilton Rating Scale for Depression (HRSD) score greater than or equal to 18
• 4. capable of providing informed consent and complying with study procedures
• 5. using appropriate contraceptive method if woman of child-bearing age

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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3 participants in 4 patient groups, including a placebo group

Clinical Frequency Management: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Research Frequency Management: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Clinical Frequency Management: Escitalopram

Active Comparator group

Description:

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.

Treatment:

Drug: Escitalopram

Research Frequency Management: Escitalopram

Active Comparator group

Description:

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

Treatment:

Drug: Escitalopram