<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/NCT02989727</url>
  </required_header>
  <id_info>
    <org_study_id>GSK-SCA100223</org_study_id>
    <nct_id>NCT02989727</nct_id>
  </id_info>
  <brief_title>Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine</brief_title>
  <official_title>Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine: Results From an 8-week, Multicenter, Double-blind, Placebo-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Saskatchewan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Saskatchewan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if patients with melancholic bipolar II depression&#xD;
      are more responsive to lamotrigine than patients with non-melancholic bipolar II depression.&#xD;
      To do this, the investigators will re-analyze a previous clinical trial that evaluated&#xD;
      lamotrigine as a treatment for bipolar II depression (GSK-SCA100223; NCT00274677).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients suffering from depression with melancholic symptoms (i.e., anhedonia, flat affect,&#xD;
      diurnal mood variation, terminal insomnia, psychomotor disturbances, decreased&#xD;
      weight/appetite, and excessive guilt) respond better to certain antidepressants. Melancholic&#xD;
      symptoms also occur in bipolar depression, although they have received less research.&#xD;
      Lamotrigine has been shown to alter some of the biological processes that are known to occur&#xD;
      in melancholic depression. The purpose of this study is to determine if patients with&#xD;
      melancholic bipolar II depression are more responsive to lamotrigine than patients with&#xD;
      non-melancholic bipolar II depression.&#xD;
&#xD;
      This study will re-analyze data from a previous 8-week, randomized, placebo-controlled trial&#xD;
      that evaluated lamotrigine as a treatment for bipolar II depression (GSK-SCA100223;&#xD;
      NCT00274677). The original study data was made available by GlaxoSmithKline as part of an&#xD;
      initiative to make clinical trials data available for research use. Access was applied for&#xD;
      via https://www.clinicalstudydatarequest.com.&#xD;
&#xD;
      The analysis strategy will be comparable to the original study, although the investigators&#xD;
      will first classify participants as suffering from either melancholic or non-melancholic&#xD;
      depression. The diagnosis of melancholic depression was established according to baseline&#xD;
      responses to the Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Åsberg&#xD;
      Depression Rating Scale (MADRS), according to the DSM-IV-TR diagnostic criteria. HAMD-17 and&#xD;
      MADRS change scores will be compared between the treatment and placebo groups using Analysis&#xD;
      of Variance (ANOVA). Both ANOVA models will include a test for an interaction between&#xD;
      treatment group (lamotrigine vs. placebo) and melancholic depression (melancholic depression&#xD;
      vs. non-melancholic depression). To handle missing data, each ANOVA model will be computed&#xD;
      with only complete-case data first and subsequently using inverse probability weights that&#xD;
      account for the probability of drop out. Inverse probability weights will be created based on&#xD;
      covariates that predict missing responses. HAMD-17 and MADRS response rates between the&#xD;
      treatment and placebo groups will be evaluated with a Cox proportional hazard regression&#xD;
      analysis. There will be two separate analyses, one including participants with melancholic&#xD;
      depression, and one including participants with non-melancholic depression. Statistical&#xD;
      models will also adjust for baseline depression severity, if participants with melancholic&#xD;
      depression are found to have more severe depressive symptoms at baseline.&#xD;
&#xD;
      Given the delay between antidepressant initiation and response, trial-and-error prescribing&#xD;
      is an inevitably lengthy process. The investigators hope the results of this study will&#xD;
      enable more timely and effective treatment for patients with bipolar depression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2003</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">August 2005</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores</measure>
    <time_frame>Eight weeks</time_frame>
    <description>Scale scores range from 0 to 60. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.&#xD;
Lower scores indicate greater improvement of depressive symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hamilton Depression Rating Scale (HAMD-17) Change Scores</measure>
    <time_frame>Eight weeks</time_frame>
    <description>Scale scores range from 0 to 52. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.&#xD;
Lower scores indicate greater improvement of depressive symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Eight weeks</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Seven weeks</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Six weeks</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Five weeks</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Four weeks</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Three weeks</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Two weeks</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>One week</time_frame>
    <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>Eight weeks</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>Seven weeks</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>Six weeks</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>Five weeks</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>Four weeks</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>Three weeks</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>Two weeks</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</measure>
    <time_frame>One week</time_frame>
    <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Depression</condition>
  <condition>Bipolar Disorder</condition>
  <condition>Bipolar Depression</condition>
  <condition>Melancholia</condition>
  <condition>Lamotrigine</condition>
  <arm_group>
    <arm_group_label>Lamotrigine - melancholic depression</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - melancholic depression</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lamotrigine - nonmelancholic depression</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - nonmelancholic depression</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lamotrigine</intervention_name>
    <description>Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
    <arm_group_label>Lamotrigine - melancholic depression</arm_group_label>
    <arm_group_label>Lamotrigine - nonmelancholic depression</arm_group_label>
    <other_name>Lamictal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebo tablets</description>
    <arm_group_label>Placebo - melancholic depression</arm_group_label>
    <arm_group_label>Placebo - nonmelancholic depression</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must provide written and informed consent.&#xD;
&#xD;
          2. Diagnosis of Bipolar II Disorder and currently depressed for minimum of the last 8&#xD;
             weeks, with a HAMD-17 score of at least 18 with scores of 3 or more on Items 1 or 7.&#xD;
&#xD;
          3. For females, be of non-childbearing potential, or of childbearing potential with a&#xD;
             negative pregnancy test at screening and agrees to one of (a) abstinence from sex two&#xD;
             weeks prior and five days after drug continuation/discontinuation, (b) personal or&#xD;
             partner sterilization, (c) one method of hormonal contraception, or (d) two barrier&#xD;
             methods of contraception.&#xD;
&#xD;
          4. Acceptable results (within two times the normal limit) on laboratory screening tests&#xD;
             (e.g., thyroid function).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active suicidality.&#xD;
&#xD;
          2. History of non-response to antidepressant treatment, or any previous treatment with&#xD;
             lamotrigine.&#xD;
&#xD;
          3. History of substance dependence in the past year, or abuse within the 4 weeks prior to&#xD;
             study entry.&#xD;
&#xD;
          4. Rapid cycling bipolar disorder.&#xD;
&#xD;
          5. Receiving additional psychoactive medication (not including lorazepam for agitation),&#xD;
             or has started a new course of psychotherapy within the last month.&#xD;
&#xD;
          6. Received treatment for an anxiety or eating disorder within the last 12 months.&#xD;
&#xD;
          7. Investigational drug use within the last month.&#xD;
&#xD;
          8. History of epilepsy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rudy C Bowen, FRCPC</last_name>
    <role>Study Director</role>
    <affiliation>University of Saskatchewan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Psychiatry, Royal University Hospital</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <zip>S7N0W8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.gov/ct2/show/record/NCT00274677</url>
    <description>The ClinicalTrials.gov posting for the original study (GSK-SCA100223; NCT00274677) from which data for the present study was obtained.</description>
  </link>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>December 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <results_first_submitted>December 27, 2017</results_first_submitted>
  <results_first_submitted_qc>September 19, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 15, 2019</results_first_posted>
  <last_update_submitted>September 19, 2018</last_update_submitted>
  <last_update_submitted_qc>September 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Saskatchewan</investigator_affiliation>
    <investigator_full_name>Evyn Peters</investigator_full_name>
    <investigator_title>Resident</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Bipolar Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lamotrigine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for the study (GSK-SCA100223; NCT00274677) is available through www.clinicalstudydatarequest.com.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study only analyzed data from treatment completers in the original study, NCT00274677. The original study enrolled 221 participants, with 150 completing the trial.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Lamotrigine - Melancholic Depression</title>
          <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
        </group>
        <group group_id="P2">
          <title>Placebo - Melancholic Depression</title>
          <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
        </group>
        <group group_id="P3">
          <title>Lamotrigine - Nonmelancholic Depression</title>
          <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
        </group>
        <group group_id="P4">
          <title>Placebo - Nonmelancholic Depression</title>
          <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="44"/>
                <participants group_id="P3" count="30"/>
                <participants group_id="P4" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="44"/>
                <participants group_id="P3" count="30"/>
                <participants group_id="P4" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lamotrigine - Melancholic Depression</title>
          <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
        </group>
        <group group_id="B2">
          <title>Placebo - Melancholic Depression</title>
          <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
        </group>
        <group group_id="B3">
          <title>Lamotrigine - Nonmelancholic Depression</title>
          <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
        </group>
        <group group_id="B4">
          <title>Placebo - Nonmelancholic Depression</title>
          <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</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="46"/>
            <count group_id="B2" value="44"/>
            <count group_id="B3" value="30"/>
            <count group_id="B4" value="30"/>
            <count group_id="B5" value="150"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="38.2" spread="12.5"/>
                    <measurement group_id="B2" value="37.8" spread="10.9"/>
                    <measurement group_id="B3" value="41.2" spread="10.6"/>
                    <measurement group_id="B4" value="35.8" spread="11.2"/>
                    <measurement group_id="B5" value="38.2" spread="11.4"/>
                  </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="31"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores</title>
        <description>Scale scores range from 0 to 60. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.&#xD;
Lower scores indicate greater improvement of depressive symptoms.</description>
        <time_frame>Eight weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores</title>
          <description>Scale scores range from 0 to 60. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.&#xD;
Lower scores indicate greater improvement of depressive symptoms.</description>
          <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="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.7" spread="10.8"/>
                    <measurement group_id="O2" value="-13.8" spread="11.6"/>
                    <measurement group_id="O3" value="-16.0" spread="10.5"/>
                    <measurement group_id="O4" value="-15.5" spread="9.93"/>
                  </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>
            <groups_desc>Weighted ANOVA models were used to compare change scores between lamotrigine and placebo groups while testing for interactions by melancholic status. The estimate and test reported is for the the interaction between treatment condition and melancholic status.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.59</p_value>
            <method>ANOVA</method>
            <param_type>ANOVA estimate</param_type>
            <param_value>1.88</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.51</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hamilton Depression Rating Scale (HAMD-17) Change Scores</title>
        <description>Scale scores range from 0 to 52. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.&#xD;
Lower scores indicate greater improvement of depressive symptoms.</description>
        <time_frame>Eight weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Hamilton Depression Rating Scale (HAMD-17) Change Scores</title>
          <description>Scale scores range from 0 to 52. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.&#xD;
Lower scores indicate greater improvement of depressive symptoms.</description>
          <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="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.5" spread="7.92"/>
                    <measurement group_id="O2" value="-10.9" spread="9.52"/>
                    <measurement group_id="O3" value="-13.0" spread="7.59"/>
                    <measurement group_id="O4" value="-10.6" spread="6.55"/>
                  </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>
            <groups_desc>Weighted ANOVA models were used to compare change scores between lamotrigine and placebo groups while testing for interactions by melancholic status. The estimate and test reported is for the the interaction between treatment condition and melancholic status.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.84</p_value>
            <method>ANOVA</method>
            <param_type>ANOVA estimate</param_type>
            <param_value>0.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>2.56</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Eight weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="16"/>
                  </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_list>
            <groups_desc>Weighted Cox regression with treatment condition (lamotrigine vs. placebo) predicting treatment response. Response is defined as a score reduction of at least 50% from baseline. The outcome variable is binary coded with &quot;1&quot; being a response at anytime point and &quot;0&quot; indicating no response.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.08</p_value>
            <method>Regression, Cox</method>
            <param_type>Cox Proportional Hazard</param_type>
            <param_value>1.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.10</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Weighted Cox regression with treatment condition (lamotrigine vs. placebo) predicting treatment response. Response is defined as a score reduction of at least 50% from baseline. The outcome variable is binary coded with &quot;1&quot; being a response at anytime point and &quot;0&quot; indicating no response.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.53</p_value>
            <method>Regression, Cox</method>
            <param_type>Cox Proportional Hazard</param_type>
            <param_value>1.08</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.12</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Seven weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Six weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Five weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="12"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Four weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="9"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Three weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Two weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
        <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>One week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Eight weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="14"/>
                  </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_list>
            <groups_desc>Weighted Cox regression with treatment condition (lamotrigine vs. placebo) predicting treatment response. Response is defined as a score reduction of at least 50% from baseline. The outcome variable is binary coded with &quot;1&quot; being a response at any time point and &quot;0&quot; indicating no response.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.02</p_value>
            <method>Regression, Cox</method>
            <param_type>Cox Proportional Hazard</param_type>
            <param_value>1.27</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.11</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Weighted Cox regression with treatment condition (lamotrigine vs. placebo) predicting treatment response. Response is defined as a score reduction of at least 50% from baseline. The outcome variable is binary coded with &quot;1&quot; being a response at any time point and &quot;0&quot; indicating no response.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.73</p_value>
            <method>Regression, Cox</method>
            <param_type>Cox Proportional Hazard</param_type>
            <param_value>1.05</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.13</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Seven weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Six weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Five weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="10"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Four weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="9"/>
                    <measurement group_id="O4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Three weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>Two weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
        <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
        <time_frame>One week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Melancholic Depression</title>
            <description>Participants with melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
          <group group_id="O3">
            <title>Lamotrigine - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.&#xD;
Lamotrigine: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Nonmelancholic Depression</title>
            <description>Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.&#xD;
Placebos: Placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)</title>
          <description>Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks.</time_frame>
      <desc>We have combined the two lamotrigine arms (melancholic and nonmelancholic) into one group, and also the two placebo arms (melancholic and nonmelancholic) into one group. We did not analyze safety data by melancholic status, so we are only able to report the original safety results (which was stratified by treatment condition but not melancholic status).</desc>
      <group_list>
        <group group_id="E1">
          <title>Lamotrigine</title>
          <description>The data is from 109 participant that were randomized in the original trial.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>The data is from 109 participant that were randomized in the original trial.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="88" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="85" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Short duration of trial in context of slow dosing regime&#xD;
Inability to assess other definitions of melancholia&#xD;
Sample of only bipolar II depression</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Evyn Peters</name_or_title>
      <organization>Univeristy of Saskatchewan</organization>
      <phone>13062904493</phone>
      <email>evyn.peters@usask.ca</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/NCT02989727
org study id: GSK-SCA100223
nct id: NCT02989727
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to determine if patients with melancholic bipolar II depression
      are more responsive to lamotrigine than patients with non-melancholic bipolar II depression.
      To do this, the investigators will re-analyze a previous clinical trial that evaluated
      lamotrigine as a treatment for bipolar II depression (GSK-SCA100223; NCT00274677).
Patients suffering from depression with melancholic symptoms (i.e., anhedonia, flat affect,
      diurnal mood variation, terminal insomnia, psychomotor disturbances, decreased
      weight/appetite, and excessive guilt) respond better to certain antidepressants. Melancholic
      symptoms also occur in bipolar depression, although they have received less research.
      Lamotrigine has been shown to alter some of the biological processes that are known to occur
      in melancholic depression. The purpose of this study is to determine if patients with
      melancholic bipolar II depression are more responsive to lamotrigine than patients with
      non-melancholic bipolar II depression.

      This study will re-analyze data from a previous 8-week, randomized, placebo-controlled trial
      that evaluated lamotrigine as a treatment for bipolar II depression (GSK-SCA100223;
      NCT00274677). The original study data was made available by GlaxoSmithKline as part of an
      initiative to make clinical trials data available for research use. Access was applied for
      via https://www.clinicalstudydatarequest.com.

      The analysis strategy will be comparable to the original study, although the investigators
      will first classify participants as suffering from either melancholic or non-melancholic
      depression. The diagnosis of melancholic depression was established according to baseline
      responses to the Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Åsberg
      Depression Rating Scale (MADRS), according to the DSM-IV-TR diagnostic criteria. HAMD-17 and
      MADRS change scores will be compared between the treatment and placebo groups using Analysis
      of Variance (ANOVA). Both ANOVA models will include a test for an interaction between
      treatment group (lamotrigine vs. placebo) and melancholic depression (melancholic depression
      vs. non-melancholic depression). To handle missing data, each ANOVA model will be computed
      with only complete-case data first and subsequently using inverse probability weights that
      account for the probability of drop out. Inverse probability weights will be created based on
      covariates that predict missing responses. HAMD-17 and MADRS response rates between the
      treatment and placebo groups will be evaluated with a Cox proportional hazard regression
      analysis. There will be two separate analyses, one including participants with melancholic
      depression, and one including participants with non-melancholic depression. Statistical
      models will also adjust for baseline depression severity, if participants with melancholic
      depression are found to have more severe depressive symptoms at baseline.

      Given the delay between antidepressant initiation and response, trial-and-error prescribing
      is an inevitably lengthy process. The investigators hope the results of this study will
      enable more timely and effective treatment for patients with bipolar depression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores
time frame: Eight weeks
description: Scale scores range from 0 to 60. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.
Lower scores indicate greater improvement of depressive symptoms.
measure: Hamilton Depression Rating Scale (HAMD-17) Change Scores
time frame: Eight weeks
description: Scale scores range from 0 to 52. This outcome is a change score calculated by subtracting Baseline from Week 8 scores.
Lower scores indicate greater improvement of depressive symptoms.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: Eight weeks
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: Seven weeks
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: Six weeks
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: Five weeks
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: Four weeks
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: Three weeks
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: Two weeks
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: One week
description: Scale scores range from 0 to 60. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: Eight weeks
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: Seven weeks
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: Six weeks
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: Five weeks
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: Four weeks
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: Three weeks
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: Two weeks
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
time frame: One week
description: Scale scores range from 0 to 52. A response is defined as a score reduction from baseline of at least 50%.
arm group label: Lamotrigine - melancholic depression
arm group type: Experimental
description: Participants with melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.
arm group label: Placebo - melancholic depression
arm group type: Placebo Comparator
description: Participants with melancholic depression who were randomly assigned to receive a placebo comparator.
arm group label: Lamotrigine - nonmelancholic depression
arm group type: Experimental
description: Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive lamotrigine tablets escalated to a target dose of 200mg/day.
arm group label: Placebo - nonmelancholic depression
arm group type: Placebo Comparator
description: Participants not meeting DSM-IV-TR diagnostic criteria for melancholic depression who were randomly assigned to receive a placebo comparator.
intervention type: Drug
intervention name: Lamotrigine
description: Lamotrigine tablets at dosages of 25mg/day for Week 1 and Week 2, 50mg/day for Week 3 and Week 4, 100mg/day for Week 5, and 200mg/day for Week 6, Week 7, and Week 8.
arm group label: Lamotrigine - melancholic depression
arm group label: Lamotrigine - nonmelancholic depression
other name: Lamictal
intervention type: Drug
intervention name: Placebos
description: Placebo tablets
arm group label: Placebo - melancholic depression
arm group label: Placebo - nonmelancholic depression
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rudy C Bowen, FRCPC
role: Study Director
affiliation: University of Saskatchewan
facility: 
country: Canada
url: https://clinicaltrials.gov/ct2/show/record/NCT00274677
description: The ClinicalTrials.gov posting for the original study (GSK-SCA100223; NCT00274677) from which data for the present study was obtained.
responsible party type: Principal Investigator
investigator affiliation: University of Saskatchewan
investigator full name: Evyn Peters
investigator title: Resident
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Bipolar Disorder
mesh term: Lamotrigine
sharing ipd: Yes
ipd description: Patient-level data for the study (GSK-SCA100223; NCT00274677) is available through www.clinicalstudydatarequest.com.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Short duration of trial in context of slow dosing regime
Inability to assess other definitions of melancholia
Sample of only bipolar II depression
point of contact: 