Developing New Clinical Management Strategies for Antidepressant Treatments
Overview
- Phase
- Phase 4
- Intervention
- Placebo
- Conditions
- Major Depressive Disorder
- Sponsor
- New York State Psychiatric Institute
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Hamilton Rating Scale for Depression
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Bret Rutherford
Clinical Professor
New York State Psychiatric Institute
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Clinical Frequency Management: 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.
Intervention: Placebo
Research Frequency Management: Placebo
Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders.
Intervention: Placebo
Clinical Frequency Management: 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.
Intervention: Escitalopram
Research Frequency Management: Escitalopram
Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders.
Intervention: Escitalopram
Outcomes
Primary Outcomes
Hamilton Rating Scale for Depression
Time Frame: Baseline week
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
Secondary Outcomes
- Hamilton Anxiety Rating Scale (HARS) 14-item Scale(Baseline week)
- CGI Severity and Improvement(Baseline week)
- Revised Life Orientation Test (LOT-R)(8 weeks)
- California Pharmacotherapy Alliance Scale (CALPAS)-Patient Version(8 weeks)
- Treatment Emergent Symptom Scale(Baseline week)
- California Pharmacotherapy Alliance Scale (CALPAS)-Clinician Version(Baseline week)
- Blind Assessment-Clinician Version(8 weeks)
- Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) 16 Item Scale(8 Weeks)
- Treatment Credibility and Expectancy Scale (CES)(8 Weeks)
- Client Satisfaction Questionnaire 8 (CSQ 8)(8 Weeks)
- Cornell Treatment Preference Index(8 weeks)
- Blind Assessment-Patient Version(8 weeks)
- Schedule for Adaptive and Nonadaptive Personality (SNAP)(8 weeks)