Major Depressive DisorderPhase 4NCT02082392
Developing New Clinical Management Strategies
A Phase 4 study testing Escitalopram in people with Major Depressive Disorder, run by New York State Psychiatric Institute at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Escitalopram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to 4 Aug 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Developing New Clinical Management Strategies for Antidepressant Treatments
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.
Read the 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.
- Conditions
- Major Depressive Disorder
- Being tested
- Escitalopram, Placebo
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
Also called Lexapro
PlaceboDrug
A substance or treatment of no intended therapeutic value in a pill form.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Escitalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline week
Secondary outcomes (13)
Hamilton Anxiety Rating Scale (HARS) 14-item Scale
Scale for anxiety symptoms administered by trained rater. The HARS 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 indi-cates mild severity, 18-24 mild to moderate severity and25-30 moderate to severe.
Measured: Baseline week
CGI Severity and Improvement
scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The CGI 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
Measured: Baseline week
Treatment Emergent Symptom Scale
rating scale for physical symptoms reported during the study. This is a standard means of recording drug-related adverse effects that will allow us to assess whether contact frequency is associated with differences in side effects among study subjects.
Measured: Baseline week
California Pharmacotherapy Alliance Scale (CALPAS)-Clinician Version
24 item Likert scale rating the clinician's assessment of the therapeutic alliance, particularly about medication issues, with the patient. This scale is superior to other therapeutic alliance scales because it is focused on drug treatment and does not contain items specific to psychotherapy. Prior studies using the CALPAS reported an association between therapeutic alliance and outcome, and some studies found alliance mediated the effect of expectancy on depression outcome.
Measured: Baseline week
Blind Assessment-Clinician Version
Rates clinician's guess as to the identity of study medication and the confidence in that guess. This assessment is necessary to document the effectiveness of the study's methods of treatment allocation concealment.
Measured: 8 weeks
Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) 16 Item Scale
rating scale for depressive symptoms based on DSM criteria. A self-report measure for depressive symptoms is valuable in this study, because it is less susceptible to clinician and rater bias. The QIDS-SR has been increasingly used in antidepressant studies (e.g., STAR*D) due to its equivalent weightings for each symptom item, clearly understandable anchor points, and inclusion of all DSM criteria for depression
Measured: 8 Weeks
Treatment Credibility and Expectancy Scale (CES)
8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement. The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies. For this study, the primary measure of expectancy will be item 4: "By the end of the treatment period, how much improvement in your depressive symptoms do you think will occur?" (0-100%).
Measured: 8 Weeks
Client Satisfaction Questionnaire 8 (CSQ 8)
self-administered scale with items rating respondents' satisfaction with mental health services they are receiving on a 4 point Likert scale. Use of the CSQ 8 will allow us to determine whether CFM and RFM are associated with differences in participant satisfaction.
Measured: 8 Weeks
Cornell Treatment Preference Index
scale used in mental health studies to document the type and strength of patients' treatment preferences. We will use a modified version in this study asking subjects "Based on your experience and how you feel right now, which of the visit frequencies in this study would be your first choice?" The strength of this preference will be measured on a 5-point Likert scale.
Measured: 8 weeks
Revised Life Orientation Test (LOT-R)
scale developed to assess individual differences in generalized optimism versus pessimism. Degree of optimism on this scale has been correlated with the magnitude of placebo response observed in studies of placebo analgesia, and we will determine whether LOT-R scores moderate effects of therapeutic contact.
Measured: 8 weeks
Schedule for Adaptive and Nonadaptive Personality (SNAP)
this questionnaire is a widely used assessment tool for personality disorders that we will also use to identify predictors of response to varying visit frequency.
Measured: 8 weeks
California Pharmacotherapy Alliance Scale (CALPAS)-Patient Version
24 item Likert scale rating the patient's assessment of the therapeutic alliance, particularly about medication issues, with the clinician. This scale is superior to other therapeutic alliance scales because it is focused on drug treatment and does not contain items specific to psychotherapy.
Measured: 8 weeks
Blind Assessment-Patient Version
rates subject's guess as to the identity of study medication and the confidence in that guess. This assessment is necessary to document the effectiveness of the study's methods of treatment allocation concealment.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2014 (estimated)
- Study startSep 2012
- Primary completionAug 2015
- Study completion4 Aug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bret Rutherford, New York State Psychiatric Institute
- Investigators
- Bret Rutherford, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02082392
- Sponsor's protocol ID
- #6652
- Status last verified
- Feb 2020
- First submitted
- 6 Mar 2014
- Last updated
- 3 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing New Clinical Management Strategies for Antidepressant Treatments
- ClinicalTrials.gov ID
- NCT02082392
- Acronym / sponsor ID
- #6652
- Conditions
- Major Depressive Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- 4 Aug 2015 (actual)
- First posted
- 10 Mar 2014 (estimated)
- Results
- Posted 7 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Clinical Frequency Management: Placebo | Placebo comparator | Drug: PlaceboStudy 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. |
| Research Frequency Management: Placebo | Placebo comparator | Drug: PlaceboWeekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. |
| Clinical Frequency Management: Escitalopram | Active comparator | Drug: EscitalopramStudy 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. |
| Research Frequency Management: Escitalopram | Active comparator | Drug: EscitalopramWeekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EscitalopramAlso: Lexapro | Drug | Clinical Frequency Management: Escitalopram, Research Frequency Management: Escitalopram |
| PlaceboA substance or treatment of no intended therapeutic value in a pill form. | Drug | Clinical Frequency Management: Placebo, Research Frequency Management: Placebo |
Primary outcome
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
13 secondary outcomes
Hamilton Anxiety Rating Scale (HARS) 14-item Scale
Time frame: Baseline week
CGI Severity and Improvement
Time frame: Baseline week
Treatment Emergent Symptom Scale
Time frame: Baseline week
California Pharmacotherapy Alliance Scale (CALPAS)-Clinician Version
Time frame: Baseline week
Blind Assessment-Clinician Version
Time frame: 8 weeks
Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) 16 Item Scale
Time frame: 8 Weeks
Treatment Credibility and Expectancy Scale (CES)
Time frame: 8 Weeks
Client Satisfaction Questionnaire 8 (CSQ 8)
Time frame: 8 Weeks
Cornell Treatment Preference Index
Time frame: 8 weeks
Revised Life Orientation Test (LOT-R)
Time frame: 8 weeks
Schedule for Adaptive and Nonadaptive Personality (SNAP)
Time frame: 8 weeks
California Pharmacotherapy Alliance Scale (CALPAS)-Patient Version
Time frame: 8 weeks
Blind Assessment-Patient Version
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bret Rutherford, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Escitalopram in people with Major Depressive Disorder, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Rating Scale for Depression (time frame: Baseline week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2020; AzTrials last refreshed its copy on 30 Oct 2026.