<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03812588</url>
  </required_header>
  <id_info>
    <org_study_id>7738</org_study_id>
    <nct_id>NCT03812588</nct_id>
  </id_info>
  <brief_title>Contact: Developing New Clinical Management Strategies</brief_title>
  <official_title>Developing New Clinical Management Strategies for Antidepressant Treatments</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Haifa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to develop new methods of administering antidepressant medications&#xD;
      that will result in improved drug/placebo separation in randomized controlled trials (RCTs)&#xD;
      for Major Depressive Disorder (MDD) and enhanced medication response in open clinical&#xD;
      treatment. The highly intensive, weekly visit schedule followed in most antidepressant RCTs&#xD;
      radically differs from how antidepressant medications are prescribed in standard clinical&#xD;
      practice and is believed to be a major reason why the majority of studies submitted to the&#xD;
      Food and Drug Administration (FDA) fail to show a significant difference between medication&#xD;
      and placebo. Moreover, a &quot;one size fits all&quot; approach to psychopharmacologic management&#xD;
      (i.e., weekly visits for all patients) does not take into account differences between&#xD;
      patients that may predispose some individuals to respond positively to frequent follow-up&#xD;
      visits, while others may respond negatively or not at all. Clinic visits comprise multiple&#xD;
      components that may be therapeutic for depression, including activating patients' behavior,&#xD;
      exposing them to medical procedures, permitting social interactions with research staff, and&#xD;
      providing supportive meetings with clinicians. Two independent meta-analyses have associated&#xD;
      more frequent study visits with increased antidepressant and placebo response as well as&#xD;
      decreased separation between medication and placebo. Despite the high costs and potential&#xD;
      disadvantages of weekly follow-up visits for patients receiving antidepressant medication,&#xD;
      this clinical management strategy has not been studied prospectively to date. It is unknown&#xD;
      whether weekly follow-up visits are needed to ensure treatment compliance and patient safety&#xD;
      in clinical trials and to what degree contacts with clinicians influence medication and&#xD;
      placebo response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study utilizes a 2 x 2, double-blind, acute, prospective design randomizing adult&#xD;
&#xD;
      outpatients with MDD to &quot;Research Frequency Management&quot; (RFM, weekly study visits) vs.&#xD;
      &quot;Community Frequency Management&quot; (CFM, every 4 weeks study visits) and antidepressant&#xD;
      medication vs. placebo. Specifying visit frequency as the independent variable in this study&#xD;
      has the distinct advantages of being easily operationalized for research purposes avoiding a&#xD;
      priori assumptions about which components of study visits influence antidepressant and&#xD;
      placebo response (i.e., behavioral activation vs. doctor-patient relationship vs. medical&#xD;
      procedures). Close monitoring of all subjects will be assured by telephone evaluations of&#xD;
      individuals randomized to CFM at intervals between monthly visits, and additional study&#xD;
      contacts will be scheduled as necessary to maintain patient safety (all extra-protocol&#xD;
      contacts will be recorded and included as a variable in outcome analyses). Additionally,&#xD;
      subjects will be characterized extensively on clinical, demographic, and psychological&#xD;
      measures to pilot the study assessment battery and search for predictor variables influencing&#xD;
      the effects of contact frequency on medication and placebo response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 30, 2019</start_date>
  <completion_date type="Actual">August 1, 2021</completion_date>
  <primary_completion_date type="Actual">May 27, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)</measure>
    <time_frame>Up to 8 Weeks</time_frame>
    <description>Scale for depressive symptoms administered by trained rater. The Hamilton 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. The scoring is based on the first 24 items of the Hamilton.&#xD;
Sum of the scores of the first 24 items (range from 0 to 74):&#xD;
0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression &gt;=23 = Very Severe Depression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale</measure>
    <time_frame>Up to 8 Weeks</time_frame>
    <description>Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety 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 &lt;17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change From Baseline Clinical Global Impressions</measure>
    <time_frame>Up to 8 Weeks</time_frame>
    <description>Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions 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.&#xD;
7-point scale: 0 = Not assessed 4 = Moderately ill&#xD;
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</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Clinical Frequency Management: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Research Frequency Management: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clinical Frequency Management: Escitalopram</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Research Frequency Management: Escitalopram</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Escitalopram</intervention_name>
    <description>Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
    <arm_group_label>Clinical Frequency Management: Escitalopram</arm_group_label>
    <arm_group_label>Research Frequency Management: Escitalopram</arm_group_label>
    <other_name>Lexapro</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
    <arm_group_label>Clinical Frequency Management: Placebo</arm_group_label>
    <arm_group_label>Research Frequency Management: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Inclusion Criteria Method of Ascertainment&#xD;
&#xD;
          1. Men and women aged 18-75 years 1. Clinical interview&#xD;
&#xD;
          2. Diagnosis with Diagnostic and Statistical Manual (DSM) V Major Depressive Disorder&#xD;
             (MDD) 2. Clinical interview, Structured Clinical Interview for DSM-V&#xD;
&#xD;
          3. 24-item Hamilton Rating Scale for Depression (HRSD) score ≥ 16 and ≤ 28; 17-item&#xD;
             Hamilton Rating Scale for Depression (HRSD) score &lt; 25 3. HRSD by trained rater&#xD;
&#xD;
          4. Capable of providing informed consent and complying with study procedures 4. Clinical&#xD;
             interview&#xD;
&#xD;
          5. Using appropriate contraceptive method if woman of child-bearing age and not currently&#xD;
             pregnant 5. Clinical interview&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current comorbid Axis I DSM V disorder other than Mild Substance Use Disorder,&#xD;
             Adjustment Disorder, Anxiety Disorder or Personality Disorder 1. Clinical interview,&#xD;
             SCID&#xD;
&#xD;
          2. Diagnosis of Moderate to Severe Substance Use Disorder within the past 12 months 2.&#xD;
             Clinical interview, SCID, Urine tox&#xD;
&#xD;
          3. present or past history of psychosis, psychotic disorder, mania, or bipolar disorder&#xD;
             3. Clinical interview, SCID&#xD;
&#xD;
          4. baseline HRSD 24-item score &gt; 28 or HRSD suicide item &gt; 2 or baseline HRSD 17-item&#xD;
             score ≥ 25 4. HRSD by trained rater&#xD;
&#xD;
          5. History of allergic or adverse reaction to escitalopram, or non-response to adequate&#xD;
             trial of escitalopram (at least 4 weeks at dose of 20mg) during the current episode 5.&#xD;
             Clinical interview&#xD;
&#xD;
          6. Current treatment with psychotherapy, antidepressants, antipsychotics, or mood&#xD;
             stabilizers 6. Clinical interview&#xD;
&#xD;
          7. CGI-Severity score of 6 or greater at baseline 7. CGI based on Clinical interview&#xD;
&#xD;
          8. Acute, severe, or unstable medical illness 8. Clinical interview, Physical Exam,&#xD;
             Screening Labs&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bret Rutherford, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <results_first_submitted>February 28, 2022</results_first_submitted>
  <results_first_submitted_qc>March 28, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 21, 2022</results_first_posted>
  <last_update_submitted>March 28, 2022</last_update_submitted>
  <last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Bret Rutherford</investigator_full_name>
    <investigator_title>Associate Professor in Clinical Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Escitalopram</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 17, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT03812588/Prot_ICF_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT03812588/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>In total, 29 subjects were enrolled. Of the 29 enrolled, 4 subjects did not continue in the study after enrolling. These 4 subjects did not appear for their randomization visit at which they would have been assigned to a study arm. Thus, 29 patients enrolled and 25 patients started.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Clinical Frequency Management: Placebo</title>
          <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
        </group>
        <group group_id="P2">
          <title>Research Frequency Management: Placebo</title>
          <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
        </group>
        <group group_id="P3">
          <title>Clinical Frequency Management: Escitalopram</title>
          <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
        </group>
        <group group_id="P4">
          <title>Research Frequency Management: Escitalopram</title>
          <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Clinical Frequency Management: Placebo</title>
          <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
        </group>
        <group group_id="B2">
          <title>Research Frequency Management: Placebo</title>
          <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
        </group>
        <group group_id="B3">
          <title>Clinical Frequency Management: Escitalopram</title>
          <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
        </group>
        <group group_id="B4">
          <title>Research Frequency Management: Escitalopram</title>
          <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="8"/>
            <count group_id="B5" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.6" spread="14.40"/>
                    <measurement group_id="B2" value="58" spread="7.26"/>
                    <measurement group_id="B3" value="58.8" spread="22.95"/>
                    <measurement group_id="B4" value="60" spread="13.77"/>
                    <measurement group_id="B5" value="58.32" spread="13.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Rating Scale for Depression</title>
          <description>Scale for depressive symptoms administered by trained rater. The Hamilton is the standard measure of depression severity for clinical trials of antidepressants and was chosen to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. The scoring is based on the first 24 items of the Hamilton.&#xD;
Sum of the scores of the first 24 items (range from 0 to 74):&#xD;
0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression &gt;=23 = Very Severe Depression</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18" spread="4.53"/>
                    <measurement group_id="B2" value="20.4" spread="2.07"/>
                    <measurement group_id="B3" value="19.6" spread="3.65"/>
                    <measurement group_id="B4" value="20.8" spread="4.43"/>
                    <measurement group_id="B5" value="19.88" spread="3.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Anxiety Rating Scale 14-item Scale</title>
          <description>Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety 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 of the 14 items is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where &lt;17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.2" spread="3.27"/>
                    <measurement group_id="B2" value="9.57" spread="2.15"/>
                    <measurement group_id="B3" value="11.4" spread="4.22"/>
                    <measurement group_id="B4" value="9.62" spread="2.83"/>
                    <measurement group_id="B5" value="10.08" spread="2.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Clinical Global Impressions Severity</title>
          <description>Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions 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.&#xD;
7-point scale: 0 = Not assessed,&#xD;
1 = Normal, not at all ill, 2 = Borderline mentally ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, 7 = Among the most extremely ill patients</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4" spread="0.71"/>
                    <measurement group_id="B2" value="4" spread="0"/>
                    <measurement group_id="B3" value="4" spread="0"/>
                    <measurement group_id="B4" value="4" spread="0.54"/>
                    <measurement group_id="B5" value="4" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)</title>
        <description>Scale for depressive symptoms administered by trained rater. The Hamilton 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. The scoring is based on the first 24 items of the Hamilton.&#xD;
Sum of the scores of the first 24 items (range from 0 to 74):&#xD;
0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression &gt;=23 = Very Severe Depression</description>
        <time_frame>Up to 8 Weeks</time_frame>
        <population>Two CFM, Placebo, two RFM, Placebo, and two CFM, Escitalopram participants did not complete the Hamilton Rating Scale for Depression at Week 8, and so their change from baseline Hamilton Rating scale for Depression score could not be calculated.</population>
        <group_list>
          <group group_id="O1">
            <title>Clinical Frequency Management: Placebo</title>
            <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
          </group>
          <group group_id="O2">
            <title>Research Frequency Management: Placebo</title>
            <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
          </group>
          <group group_id="O3">
            <title>Clinical Frequency Management: Escitalopram</title>
            <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
          </group>
          <group group_id="O4">
            <title>Research Frequency Management: Escitalopram</title>
            <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)</title>
          <description>Scale for depressive symptoms administered by trained rater. The Hamilton 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. The scoring is based on the first 24 items of the Hamilton.&#xD;
Sum of the scores of the first 24 items (range from 0 to 74):&#xD;
0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression &gt;=23 = Very Severe Depression</description>
          <population>Two CFM, Placebo, two RFM, Placebo, and two CFM, Escitalopram participants did not complete the Hamilton Rating Scale for Depression at Week 8, and so their change from baseline Hamilton Rating scale for Depression score could not be calculated.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.33" spread="3.51"/>
                    <measurement group_id="O2" value="11.4" spread="4.04"/>
                    <measurement group_id="O3" value="5.33" spread="13.65"/>
                    <measurement group_id="O4" value="9.25" spread="9.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.292</p_value>
            <p_value_desc>Linear regression model of condition in predicting change in HRSD-24. P-value and coefficient are Medication:Track. Medication (Escitalopram or Placebo) with Track (RFM or CFM) as co-variates. The threshold for statistical significance was p&gt;0.05.</p_value_desc>
            <method>Regression, Linear</method>
            <param_type>Slope</param_type>
            <param_value>7.900</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>7.261</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale</title>
        <description>Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety 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 &lt;17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.</description>
        <time_frame>Up to 8 Weeks</time_frame>
        <population>Two CFM, Placebo, two RFM, Placebo, and three CFM, Escitalopram participants did not complete the Hamilton Anxiety at Week 8, and so their change from baseline Hamilton Anxiety score could not be calculated.</population>
        <group_list>
          <group group_id="O1">
            <title>Clinical Frequency Management: Placebo</title>
            <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
          </group>
          <group group_id="O2">
            <title>Research Frequency Management: Placebo</title>
            <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
          </group>
          <group group_id="O3">
            <title>Clinical Frequency Management: Escitalopram</title>
            <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
          </group>
          <group group_id="O4">
            <title>Research Frequency Management: Escitalopram</title>
            <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale</title>
          <description>Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety 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 &lt;17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.</description>
          <population>Two CFM, Placebo, two RFM, Placebo, and three CFM, Escitalopram participants did not complete the Hamilton Anxiety at Week 8, and so their change from baseline Hamilton Anxiety score could not be calculated.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.67" spread="2.52"/>
                    <measurement group_id="O2" value="4.40" spread="4.22"/>
                    <measurement group_id="O3" value="6.50" spread="4.95"/>
                    <measurement group_id="O4" value="3.37" spread="4.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline Clinical Global Impressions</title>
        <description>Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions 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.&#xD;
7-point scale: 0 = Not assessed 4 = Moderately ill&#xD;
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</description>
        <time_frame>Up to 8 Weeks</time_frame>
        <population>Two CFM, Placebo, two RFM, Placebo, and two CFM, Escitalopram participants did not complete the CGI at Week 8, and so their change from baseline CGI score could not be calculated.</population>
        <group_list>
          <group group_id="O1">
            <title>Clinical Frequency Management: Placebo</title>
            <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
          </group>
          <group group_id="O2">
            <title>Research Frequency Management: Placebo</title>
            <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
          </group>
          <group group_id="O3">
            <title>Clinical Frequency Management: Escitalopram</title>
            <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
          </group>
          <group group_id="O4">
            <title>Research Frequency Management: Escitalopram</title>
            <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Clinical Global Impressions</title>
          <description>Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions 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.&#xD;
7-point scale: 0 = Not assessed 4 = Moderately ill&#xD;
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</description>
          <population>Two CFM, Placebo, two RFM, Placebo, and two CFM, Escitalopram participants did not complete the CGI at Week 8, and so their change from baseline CGI score could not be calculated.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" spread="1.73"/>
                    <measurement group_id="O2" value="1.20" spread="0.84"/>
                    <measurement group_id="O3" value="0.67" spread="1.15"/>
                    <measurement group_id="O4" value="1.50" spread="1.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Subjects were monitored over a period of 8 weeks.</time_frame>
      <desc>Subjects in the CFM group were evaluated by study personnel no less frequently than every 2 weeks for 8 weeks. Subjects were monitored for adverse effects, and dose adjustments will be made if indicated during this period of time.</desc>
      <group_list>
        <group group_id="E1">
          <title>Clinical Frequency Management: Placebo</title>
          <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
        </group>
        <group group_id="E2">
          <title>Research Frequency Management: Placebo</title>
          <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.</description>
        </group>
        <group group_id="E3">
          <title>Clinical Frequency Management: Escitalopram</title>
          <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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
        </group>
        <group group_id="E4">
          <title>Research Frequency Management: Escitalopram</title>
          <description>Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.&#xD;
Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="15" subjects_affected="4" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Body Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Diaphoresis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="6" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Weight Gain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Excitement</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Memory Loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vivid Dreams</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Frequency/Urgency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Orgasm Delay</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="4" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Shortness of Breath</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to challenges associated with the pandemic, the study was completed with a smaller sample size than originally intended.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Bret Rutherford</name_or_title>
      <organization>New York State Psychiatric Institute</organization>
      <phone>646-774-8660</phone>
      <email>bret.rutherford@nyspi.columbia.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03812588
org study id: 7738
nct id: NCT03812588
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)
time frame: Up to 8 Weeks
description: Scale for depressive symptoms administered by trained rater. The Hamilton 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. The scoring is based on the first 24 items of the Hamilton.
Sum of the scores of the first 24 items (range from 0 to 74):
0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression >=23 = Very Severe Depression
measure: Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale
time frame: Up to 8 Weeks
description: Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety 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 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
measure: Change From Baseline Clinical Global Impressions
time frame: Up to 8 Weeks
description: Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions 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
arm group label: Clinical Frequency Management: Placebo
arm group type: Placebo Comparator
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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.
arm group label: Research Frequency Management: Placebo
arm group type: Placebo Comparator
description: Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.
arm group label: Clinical Frequency Management: Escitalopram
arm group type: Active Comparator
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. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.
arm group label: Research Frequency Management: Escitalopram
arm group type: Active Comparator
description: Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.
intervention type: Drug
intervention name: Escitalopram
description: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.
arm group label: Clinical Frequency Management: Escitalopram
arm group label: Research Frequency Management: Escitalopram
other name: Lexapro
intervention type: Drug
intervention name: Placebo
description: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.
arm group label: Clinical Frequency Management: Placebo
arm group label: Research Frequency Management: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Bret Rutherford, MD
role: Principal Investigator
affiliation: New York State Psychiatric Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Bret Rutherford
investigator title: Associate Professor in Clinical Psychiatry
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Escitalopram
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to challenges associated with the pandemic, the study was completed with a smaller sample size than originally intended.
point of contact: 