<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/NCT02234362</url>
  </required_header>
  <id_info>
    <org_study_id>2014P001812</org_study_id>
    <nct_id>NCT02234362</nct_id>
  </id_info>
  <brief_title>Vortioxetine for Menopausal Depression</brief_title>
  <official_title>Vortioxetine for Menopausal Depression and Associated Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda Pharmaceuticals North America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The broad goal of this study was to examine the efficacy and tolerability of vortioxetine&#xD;
      (flexible dose) for the treatment of major depressive disorder (MDD) in symptomatic women&#xD;
      around the menopausal transition. We hypothesized that an eight-week treatment with&#xD;
      vortioxetine would promote a significant improvement of depression symptoms and other&#xD;
      menopause-related physical symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Forty-seven peri- and postmenopausal women were enrolled in this open-label study. This was&#xD;
      an 8-week intervention using open-label vortioxetine with flexible dose between 5-20 mg,&#xD;
      dependent on participant response and tolerability. In addition to assessment of depressive&#xD;
      symptoms, improvement of menopause-related physical and emotional symptoms that occur with&#xD;
      MDD, including vasomotor symptoms, cognition, fatigue, anxiety, sleep complaints, and quality&#xD;
      of life, were also examined.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 12, 2015</start_date>
  <completion_date type="Actual">September 29, 2016</completion_date>
  <primary_completion_date type="Actual">September 29, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Montgomery-Asberg Depression Rating Scale Score (MADRS) at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>The efficacy of vortioxetine for trea-ting depressive symptoms was measured by mean change in Montgomery-Asberg Depression Rating Scale (MADRS) depression score from Baseline (Visit 1) to Week 8 (Visit 5). The MADRS score was assessed at every study visit (Visits 1-5). Participants were considered to have responded to vortioxetine if their MADRS score was reduced by 50% or more from baseline to the end of treatment, and to be in remission if their final MADRS score was less than 10. Higher MADRS score indicates more severe depression. The overall MADRS score ranges from 0 to 60.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Daytime at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vasomotor Symptoms (VMS) Severity During Daytime at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.&#xD;
Severity of VMS:&#xD;
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Nighttime at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vasomotor Symptoms (VMS) Severity During Nighttime at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.&#xD;
Severity of VMS:&#xD;
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Cognitive and Physical Functioning Questionnaire (CPFQ) Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Cognition and physical functioning was measured by self-report responses to Cognitive and Physical Functioning Questionnaire (CPFQ).The range of scores is from 7-42. Higher scores indicate lower cognitive and executive functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Beck Anxiety Inventory (BAI) Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Anxiety was measured by self-report responses to Beck Anxiety Inventory (BAI). It is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in children and adults. Several studies have found the Beck Anxiety Inventory to be an accurate measure of anxiety symptoms in children and adults. Higher scores on the BAI indicate more anxiety symptoms. The range of BAI scores is from 0 to 63, with 0-9=Minimal anxiety, 10-16=Mild anxiety, 17-29=Moderate anxiety, and 30-63=Severe anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Sleep quality and disturbances during the past month were assessed with the Pittsburgh Sleep Quality Index (PSQI). The PSQI also incorporates daytime functioning into the total score. In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. The range of scores is 0-21.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Menopause Specific Quality of Life (MENQOL) Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Quality of life, menopause-specific, is assessed by the Menopause Specific Quality of Life (MENQOL).&#xD;
The MENQOL is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor (items 1-3), psychosocial (items 4-10), physical (items 11-26), and sexual (items 27-29). Items pertaining to a specific symptom are rated as present or not present, and if present, how bothersome on a zero (not bothersome) to six (extremely bothersome) scale. Means are computed for each subscale by dividing the sum of the domain's items by the number of items within that domain. Non-endorsement of an item is scored a &quot;1&quot; and endorsement a &quot;2&quot;, plus the number of the particular rating, so that the possible score on any item ranges from 1-8. Total score also ranges from 1-8. Higher scores indicate that menopause symptoms are more bothersome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression-Fatigue (CGI-F) Scale Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Fatigue symptoms were assessed by the Clinical Global Impression-Fatigue (CGI-F) scale.The CGI-F is a single item global assessment scales to specifically evaluate symptoms of fatigue. Higher scores indicate more fatigue symptoms. The range of scores is from 0-7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Severity of illness was assessed by the Clinical Global Impression-Severity (CGI-S) Scale. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. The range of scores is 0-7. Higher scores indicate greater severity of illness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pain Assessment (PEG) Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Pain symptoms were assessed by the Pain Assessment (PEG). The PEG is a three-item scale assessing pain intensity and interference. A higher score indicates more pain symptoms. The range of scores is from 0 to 30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Greene Climacteric Scale (GCS) Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Menopause related symptoms were assessed using the Greene Climacteric Scale (GCS). The Greene Scale provides a brief measure of menopause symptoms. It can be used to assess changes in different symptoms, before and after menopause treatment. Three main areas are measured:&#xD;
1. Psychological (items 1-11). 2. Physical (items 12-18). 3. Vasomotor (items 19, 20).&#xD;
A higher score indicates that menopause symptoms are more bothersome. The range of scores is from 0 to 63.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Digit Symbol Substitution Test (DSST) Score at Week 8 (Visit 5)</measure>
    <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
    <description>Processing speed, working memory, visuospatial processing and attention was assessed by the Digit Symbol Substitution Test (DSST).&#xD;
The DSST test requires the examinee to transcribe a unique geometric symbol with its corresponding Arabic number. The examinee is initially shown a key containing the numbers from 1 to 9. Under each number there is a corresponding geometric symbol. The examinee is then shown a series of boxes containing numbers in the top boxes, and blank boxes below them. After a short practice trial, they are then asked to copy the corresponding geometric symbol under each number. The raw score is the number of correct items completed within the prescribed time limit. Higher scores indicate faster processing speed, working memory, and visuospatial processing and attention. The range of scores is 0-63.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Depression</condition>
  <condition>Menopause</condition>
  <condition>Vasomotor Disturbance</condition>
  <condition>Hot Flashes</condition>
  <condition>Sleep</condition>
  <arm_group>
    <arm_group_label>open-label vortioxetine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>flexible-dose vortioxetine of 5-20 mg depending on tolerability</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vortioxetine</intervention_name>
    <description>Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
    <arm_group_label>open-label vortioxetine</arm_group_label>
    <other_name>Trintellix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women aged 40-62 years who are perimenopausal or early postmenopausal (within 5 years&#xD;
             of the last menstrual period if not surgically postmenopausal), including:&#xD;
&#xD;
               1. Perimenopausal women who have experienced changes in menstrual cycle frequency or&#xD;
                  duration, and/or physical symptoms indicative of menopausal transition, as&#xD;
                  determined by clinician&#xD;
&#xD;
               2. Women who are using the Mirena Intrauterine Device (IUD), with&#xD;
                  Follicle-stimulating hormone (FSH) level &gt; 20 milli-International unit/ml&#xD;
                  (mIU/mL)&#xD;
&#xD;
          2. Women meeting Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV)&#xD;
             criteria for major depression (assessed by the Mini International Neuropsychiatric&#xD;
             Interview - M.I.N.I.)&#xD;
&#xD;
          3. MADRS scores of at least 20 at baseline visit&#xD;
&#xD;
          4. Women with significant menopause-related physical symptoms, indicated by any of the&#xD;
             following criteria:&#xD;
&#xD;
               1. Greene Climacteric Scale total scores &gt; 20;&#xD;
&#xD;
               2. Greene Climacteric Scale sub-score for vasomotor symptoms &gt;3;&#xD;
&#xD;
               3. 14 or more bothersome hot flashes per week (self-reported).&#xD;
&#xD;
          5. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnancy (determined by urine pregnancy test), intending pregnancy, or breast&#xD;
             feeding.&#xD;
&#xD;
          2. Women whose primary diagnosis is Panic Disorder, Obsessive Compulsive Disorder (OCD),&#xD;
             Generalized Anxiety Disorder (GAD), Seasonal Affective Disorder (SAD), or any other&#xD;
             Axis I pathology active within 6 months prior to screening visit (except for specific&#xD;
             phobias). Anxiety disorders are allowable if secondary to MDD as the primary&#xD;
             diagnosis.&#xD;
&#xD;
          3. History of or current mania/hypomania, psychosis, or bipolar disorder&#xD;
&#xD;
          4. Regular treatment with an Selective Serotonin Reuptake Inhibitor (SSRI) or Selective&#xD;
             Norepinephrine Reuptake Inhibitors (SNRI) within 2 months prior to screening visit&#xD;
&#xD;
          5. Serious suicidal ideation or intent&#xD;
&#xD;
          6. Women who have used psychoactive or centrally acting medications within 2 weeks prior&#xD;
             to study screening&#xD;
&#xD;
          7. Women who have received hormonal intervention within 1 month prior to study entry&#xD;
&#xD;
          8. Known hypersensitivity to vortioxetine or any of the inactive ingredients&#xD;
&#xD;
          9. Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization or&#xD;
             potential need to use an MAOI during the study or within 21 days of discontinuation of&#xD;
             study drug&#xD;
&#xD;
         10. Treatment with linezolid or intravenous methylene blue&#xD;
&#xD;
         11. Patients with severe hepatic impairment&#xD;
&#xD;
         12. Uncontrolled hypertension (&gt;160/90 mmHg)&#xD;
&#xD;
         13. Resting heart rate &gt;110/minute&#xD;
&#xD;
         14. Any current severe or unstable medical illness&#xD;
&#xD;
         15. Not using a medically approved method of birth control, if sexually active and not 12&#xD;
             or more months since last menstrual period&#xD;
&#xD;
         16. Drug or alcohol abuse in the past 1 year&#xD;
&#xD;
         17. Use of any disallowed medications (specified in the Excluded Concomitant Medication&#xD;
             section below)&#xD;
&#xD;
         18. Concurrent enrollment in another clinical trial&#xD;
&#xD;
        Excluded Concomitant Medications:&#xD;
&#xD;
          -  Selective estrogen-receptor modulators (SERMs)&#xD;
&#xD;
          -  Hormone replacement therapy&#xD;
&#xD;
          -  Hormonal contraceptives, excluding Mirena IUD&#xD;
&#xD;
          -  Natural menopause supplements&#xD;
&#xD;
          -  Episodic sleep medications (chronic, regular, stable-dose benzodiazepines are allowed)&#xD;
&#xD;
          -  Antidepressants&#xD;
&#xD;
          -  Phytoestrogens&#xD;
&#xD;
          -  Soy-based medications&#xD;
&#xD;
          -  Steroids&#xD;
&#xD;
          -  Anorectics, appetite depressants&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>62 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marlene P Freeman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12.</citation>
    <PMID>21486038</PMID>
  </reference>
  <reference>
    <citation>Bromberger JT, Assmann SF, Avis NE, Schocken M, Kravitz HM, Cordal A. Persistent mood symptoms in a multiethnic community cohort of pre- and perimenopausal women. Am J Epidemiol. 2003 Aug 15;158(4):347-56. doi: 10.1093/aje/kwg155.</citation>
    <PMID>12915500</PMID>
  </reference>
  <reference>
    <citation>Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000 Dec 16;356(9247):2059-63. doi: 10.1016/S0140-6736(00)03403-6.</citation>
    <PMID>11145492</PMID>
  </reference>
  <reference>
    <citation>Pehrson AL, Cremers T, Betry C, van der Hart MG, Jorgensen L, Madsen M, Haddjeri N, Ebert B, Sanchez C. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters--a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol. 2013 Feb;23(2):133-45. doi: 10.1016/j.euroneuro.2012.04.006. Epub 2012 May 20.</citation>
    <PMID>22612991</PMID>
  </reference>
  <reference>
    <citation>Pehrson AL, Sanchez C. Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS Spectr. 2014 Apr;19(2):121-33. doi: 10.1017/S1092852913000540. Epub 2013 Aug 1.</citation>
    <PMID>23903233</PMID>
  </reference>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <results_first_submitted>January 27, 2017</results_first_submitted>
  <results_first_submitted_qc>March 21, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 2, 2017</results_first_posted>
  <last_update_submitted>June 26, 2017</last_update_submitted>
  <last_update_submitted_qc>June 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Marlene P. Freeman, MD</investigator_full_name>
    <investigator_title>Associate Director, Center for Women's Mental Health</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hot Flashes</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vortioxetine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited through advertisements in the greater Boston metropolitan area.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Open-label Vortioxetine</title>
          <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least One Dose of Medication</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not eligible after first screening visit</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Open-label Vortioxetine</title>
          <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52.1" spread="4.8"/>
                  </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="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Highest Level of Education</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Some high school</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>High school or received GED</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Vocational/training school after high school</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Some college or Associate Degree</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Graduated college (BA, BS)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Master's Degree</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Doctoral Degree (PhD, MD, etc.)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Employment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Full-or part-time work</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Homemaker</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Disabled</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not working, unemployed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Student</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Volunteer</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Retired</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Temporary work</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Marital Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Married</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Separated/divorced/widowed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Never married/single</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Decline to answer</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Menopausal Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Perimenopausal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Naturally postmenopausal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Surgically postmenopausal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past hormone therapy use</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Used hormone therapy in the past</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Never used hormone therapy in the past</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Montgomery-Asberg Depression Rating Scale Score (MADRS) at Week 8 (Visit 5)</title>
        <description>The efficacy of vortioxetine for trea-ting depressive symptoms was measured by mean change in Montgomery-Asberg Depression Rating Scale (MADRS) depression score from Baseline (Visit 1) to Week 8 (Visit 5). The MADRS score was assessed at every study visit (Visits 1-5). Participants were considered to have responded to vortioxetine if their MADRS score was reduced by 50% or more from baseline to the end of treatment, and to be in remission if their final MADRS score was less than 10. Higher MADRS score indicates more severe depression. The overall MADRS score ranges from 0 to 60.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all 24 participants who initiated medication treatment and returned for at least one assessment after starting vortioxetine. A last observation carried forward (LOCF) analysis was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Montgomery-Asberg Depression Rating Scale Score (MADRS) at Week 8 (Visit 5)</title>
          <description>The efficacy of vortioxetine for trea-ting depressive symptoms was measured by mean change in Montgomery-Asberg Depression Rating Scale (MADRS) depression score from Baseline (Visit 1) to Week 8 (Visit 5). The MADRS score was assessed at every study visit (Visits 1-5). Participants were considered to have responded to vortioxetine if their MADRS score was reduced by 50% or more from baseline to the end of treatment, and to be in remission if their final MADRS score was less than 10. Higher MADRS score indicates more severe depression. The overall MADRS score ranges from 0 to 60.</description>
          <population>The analyzable population includes all 24 participants who initiated medication treatment and returned for at least one assessment after starting vortioxetine. A last observation carried forward (LOCF) analysis was used.</population>
          <units>units 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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.8" spread="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Daytime at Week 8 (Visit 5)</title>
        <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Daytime at Week 8 (Visit 5)</title>
          <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
          <units>hot flashes per day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.33" spread="1.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vasomotor Symptoms (VMS) Severity During Daytime at Week 8 (Visit 5)</title>
        <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.&#xD;
Severity of VMS:&#xD;
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vasomotor Symptoms (VMS) Severity During Daytime at Week 8 (Visit 5)</title>
          <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.&#xD;
Severity of VMS:&#xD;
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
          <units>units 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="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.28" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Nighttime at Week 8 (Visit 5)</title>
        <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Nighttime at Week 8 (Visit 5)</title>
          <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
          <units>hot flashes per night</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.15" spread="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vasomotor Symptoms (VMS) Severity During Nighttime at Week 8 (Visit 5)</title>
        <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.&#xD;
Severity of VMS:&#xD;
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vasomotor Symptoms (VMS) Severity During Nighttime at Week 8 (Visit 5)</title>
          <description>Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.&#xD;
Severity of VMS:&#xD;
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation who also reported having hot flashes at baseline.</population>
          <units>units 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="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.27" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Cognitive and Physical Functioning Questionnaire (CPFQ) Score at Week 8 (Visit 5)</title>
        <description>Cognition and physical functioning was measured by self-report responses to Cognitive and Physical Functioning Questionnaire (CPFQ).The range of scores is from 7-42. Higher scores indicate lower cognitive and executive functioning.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Cognitive and Physical Functioning Questionnaire (CPFQ) Score at Week 8 (Visit 5)</title>
          <description>Cognition and physical functioning was measured by self-report responses to Cognitive and Physical Functioning Questionnaire (CPFQ).The range of scores is from 7-42. Higher scores indicate lower cognitive and executive functioning.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13" lower_limit="-15" upper_limit="-7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Beck Anxiety Inventory (BAI) Score at Week 8 (Visit 5)</title>
        <description>Anxiety was measured by self-report responses to Beck Anxiety Inventory (BAI). It is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in children and adults. Several studies have found the Beck Anxiety Inventory to be an accurate measure of anxiety symptoms in children and adults. Higher scores on the BAI indicate more anxiety symptoms. The range of BAI scores is from 0 to 63, with 0-9=Minimal anxiety, 10-16=Mild anxiety, 17-29=Moderate anxiety, and 30-63=Severe anxiety.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Beck Anxiety Inventory (BAI) Score at Week 8 (Visit 5)</title>
          <description>Anxiety was measured by self-report responses to Beck Anxiety Inventory (BAI). It is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in children and adults. Several studies have found the Beck Anxiety Inventory to be an accurate measure of anxiety symptoms in children and adults. Higher scores on the BAI indicate more anxiety symptoms. The range of BAI scores is from 0 to 63, with 0-9=Minimal anxiety, 10-16=Mild anxiety, 17-29=Moderate anxiety, and 30-63=Severe anxiety.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7" lower_limit="-12.5" upper_limit="-0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 8 (Visit 5)</title>
        <description>Sleep quality and disturbances during the past month were assessed with the Pittsburgh Sleep Quality Index (PSQI). The PSQI also incorporates daytime functioning into the total score. In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. The range of scores is 0-21.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 8 (Visit 5)</title>
          <description>Sleep quality and disturbances during the past month were assessed with the Pittsburgh Sleep Quality Index (PSQI). The PSQI also incorporates daytime functioning into the total score. In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. The range of scores is 0-21.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5" lower_limit="-7.5" upper_limit="-2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Menopause Specific Quality of Life (MENQOL) Score at Week 8 (Visit 5)</title>
        <description>Quality of life, menopause-specific, is assessed by the Menopause Specific Quality of Life (MENQOL).&#xD;
The MENQOL is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor (items 1-3), psychosocial (items 4-10), physical (items 11-26), and sexual (items 27-29). Items pertaining to a specific symptom are rated as present or not present, and if present, how bothersome on a zero (not bothersome) to six (extremely bothersome) scale. Means are computed for each subscale by dividing the sum of the domain's items by the number of items within that domain. Non-endorsement of an item is scored a &quot;1&quot; and endorsement a &quot;2&quot;, plus the number of the particular rating, so that the possible score on any item ranges from 1-8. Total score also ranges from 1-8. Higher scores indicate that menopause symptoms are more bothersome.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Menopause Specific Quality of Life (MENQOL) Score at Week 8 (Visit 5)</title>
          <description>Quality of life, menopause-specific, is assessed by the Menopause Specific Quality of Life (MENQOL).&#xD;
The MENQOL is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor (items 1-3), psychosocial (items 4-10), physical (items 11-26), and sexual (items 27-29). Items pertaining to a specific symptom are rated as present or not present, and if present, how bothersome on a zero (not bothersome) to six (extremely bothersome) scale. Means are computed for each subscale by dividing the sum of the domain's items by the number of items within that domain. Non-endorsement of an item is scored a &quot;1&quot; and endorsement a &quot;2&quot;, plus the number of the particular rating, so that the possible score on any item ranges from 1-8. Total score also ranges from 1-8. Higher scores indicate that menopause symptoms are more bothersome.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.74" lower_limit="-2.61" upper_limit="-1.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression-Fatigue (CGI-F) Scale Score at Week 8 (Visit 5)</title>
        <description>Fatigue symptoms were assessed by the Clinical Global Impression-Fatigue (CGI-F) scale.The CGI-F is a single item global assessment scales to specifically evaluate symptoms of fatigue. Higher scores indicate more fatigue symptoms. The range of scores is from 0-7.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression-Fatigue (CGI-F) Scale Score at Week 8 (Visit 5)</title>
          <description>Fatigue symptoms were assessed by the Clinical Global Impression-Fatigue (CGI-F) scale.The CGI-F is a single item global assessment scales to specifically evaluate symptoms of fatigue. Higher scores indicate more fatigue symptoms. The range of scores is from 0-7.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1" lower_limit="-2.5" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score at Week 8 (Visit 5)</title>
        <description>Severity of illness was assessed by the Clinical Global Impression-Severity (CGI-S) Scale. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. The range of scores is 0-7. Higher scores indicate greater severity of illness.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score at Week 8 (Visit 5)</title>
          <description>Severity of illness was assessed by the Clinical Global Impression-Severity (CGI-S) Scale. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. The range of scores is 0-7. Higher scores indicate greater severity of illness.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1" lower_limit="-2.5" upper_limit="-1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pain Assessment (PEG) Score at Week 8 (Visit 5)</title>
        <description>Pain symptoms were assessed by the Pain Assessment (PEG). The PEG is a three-item scale assessing pain intensity and interference. A higher score indicates more pain symptoms. The range of scores is from 0 to 30.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pain Assessment (PEG) Score at Week 8 (Visit 5)</title>
          <description>Pain symptoms were assessed by the Pain Assessment (PEG). The PEG is a three-item scale assessing pain intensity and interference. A higher score indicates more pain symptoms. The range of scores is from 0 to 30.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4" lower_limit="-9.5" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Greene Climacteric Scale (GCS) Score at Week 8 (Visit 5)</title>
        <description>Menopause related symptoms were assessed using the Greene Climacteric Scale (GCS). The Greene Scale provides a brief measure of menopause symptoms. It can be used to assess changes in different symptoms, before and after menopause treatment. Three main areas are measured:&#xD;
1. Psychological (items 1-11). 2. Physical (items 12-18). 3. Vasomotor (items 19, 20).&#xD;
A higher score indicates that menopause symptoms are more bothersome. The range of scores is from 0 to 63.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Greene Climacteric Scale (GCS) Score at Week 8 (Visit 5)</title>
          <description>Menopause related symptoms were assessed using the Greene Climacteric Scale (GCS). The Greene Scale provides a brief measure of menopause symptoms. It can be used to assess changes in different symptoms, before and after menopause treatment. Three main areas are measured:&#xD;
1. Psychological (items 1-11). 2. Physical (items 12-18). 3. Vasomotor (items 19, 20).&#xD;
A higher score indicates that menopause symptoms are more bothersome. The range of scores is from 0 to 63.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.5" lower_limit="-25" upper_limit="-13.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Digit Symbol Substitution Test (DSST) Score at Week 8 (Visit 5)</title>
        <description>Processing speed, working memory, visuospatial processing and attention was assessed by the Digit Symbol Substitution Test (DSST).&#xD;
The DSST test requires the examinee to transcribe a unique geometric symbol with its corresponding Arabic number. The examinee is initially shown a key containing the numbers from 1 to 9. Under each number there is a corresponding geometric symbol. The examinee is then shown a series of boxes containing numbers in the top boxes, and blank boxes below them. After a short practice trial, they are then asked to copy the corresponding geometric symbol under each number. The raw score is the number of correct items completed within the prescribed time limit. Higher scores indicate faster processing speed, working memory, and visuospatial processing and attention. The range of scores is 0-63.</description>
        <time_frame>Baseline and Week 8 (Visit 5)</time_frame>
        <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Vortioxetine</title>
            <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Digit Symbol Substitution Test (DSST) Score at Week 8 (Visit 5)</title>
          <description>Processing speed, working memory, visuospatial processing and attention was assessed by the Digit Symbol Substitution Test (DSST).&#xD;
The DSST test requires the examinee to transcribe a unique geometric symbol with its corresponding Arabic number. The examinee is initially shown a key containing the numbers from 1 to 9. Under each number there is a corresponding geometric symbol. The examinee is then shown a series of boxes containing numbers in the top boxes, and blank boxes below them. After a short practice trial, they are then asked to copy the corresponding geometric symbol under each number. The raw score is the number of correct items completed within the prescribed time limit. Higher scores indicate faster processing speed, working memory, and visuospatial processing and attention. The range of scores is 0-63.</description>
          <population>The analyzable population includes all participants who initiated treatment with vortioxetine and returned for at least one assessment after study medication initiation.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" lower_limit="4.5" upper_limit="15.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were assessed from baseline through Week 8 (Visit 5) of the study. At each study visit, physician investigators prompted the participant to report any occurrences of health problems other than usual menopause related symptoms. Any serious or non-serious adverse events were recorded in the participant's study binder at each examination.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Open-label Vortioxetine</title>
          <description>Flexible-dose vortioxetine of 5-20 mg depending on tolerability&#xD;
Vortioxetine: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.</description>
        </group>
      </group_list>
      <serious_events>
        <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="27"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Stomach cramps</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Increased thirst</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Abdomen tenderness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Disrupted sleep</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Difficulty falling asleep</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Increased fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Edginess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headaches</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Numbness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Increased Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased libido</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Anorgasmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Mild rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Itching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Hair loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
              </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>lack of control group (important given that previous VMS medication trials have indicated modest placebo response rates, and it is difficult to determine whether the side effects are associated with the medication)&#xD;
small sample size</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Marlene Freeman</name_or_title>
      <organization>MGH Center for Women's Mental Health</organization>
      <phone>617-723-6403</phone>
      <email>mfreeman@partners.org</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/NCT02234362
org study id: 2014P001812
nct id: NCT02234362
lead sponsor: 
collaborator: 
has dmc: No
The broad goal of this study was to examine the efficacy and tolerability of vortioxetine
      (flexible dose) for the treatment of major depressive disorder (MDD) in symptomatic women
      around the menopausal transition. We hypothesized that an eight-week treatment with
      vortioxetine would promote a significant improvement of depression symptoms and other
      menopause-related physical symptoms.
Forty-seven peri- and postmenopausal women were enrolled in this open-label study. This was
      an 8-week intervention using open-label vortioxetine with flexible dose between 5-20 mg,
      dependent on participant response and tolerability. In addition to assessment of depressive
      symptoms, improvement of menopause-related physical and emotional symptoms that occur with
      MDD, including vasomotor symptoms, cognition, fatigue, anxiety, sleep complaints, and quality
      of life, were also examined.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Montgomery-Asberg Depression Rating Scale Score (MADRS) at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: The efficacy of vortioxetine for trea-ting depressive symptoms was measured by mean change in Montgomery-Asberg Depression Rating Scale (MADRS) depression score from Baseline (Visit 1) to Week 8 (Visit 5). The MADRS score was assessed at every study visit (Visits 1-5). Participants were considered to have responded to vortioxetine if their MADRS score was reduced by 50% or more from baseline to the end of treatment, and to be in remission if their final MADRS score was less than 10. Higher MADRS score indicates more severe depression. The overall MADRS score ranges from 0 to 60.
measure: Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Daytime at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.
measure: Change From Baseline in Vasomotor Symptoms (VMS) Severity During Daytime at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.
Severity of VMS:
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe
measure: Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Nighttime at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.
measure: Change From Baseline in Vasomotor Symptoms (VMS) Severity During Nighttime at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night.
Severity of VMS:
The range of scores for severity of VMS is 0-2, with higher scores indicating greater severity. 0=mild, 1=moderate, 2=severe
measure: Change From Baseline in Cognitive and Physical Functioning Questionnaire (CPFQ) Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Cognition and physical functioning was measured by self-report responses to Cognitive and Physical Functioning Questionnaire (CPFQ).The range of scores is from 7-42. Higher scores indicate lower cognitive and executive functioning.
measure: Change From Baseline in Beck Anxiety Inventory (BAI) Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Anxiety was measured by self-report responses to Beck Anxiety Inventory (BAI). It is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in children and adults. Several studies have found the Beck Anxiety Inventory to be an accurate measure of anxiety symptoms in children and adults. Higher scores on the BAI indicate more anxiety symptoms. The range of BAI scores is from 0 to 63, with 0-9=Minimal anxiety, 10-16=Mild anxiety, 17-29=Moderate anxiety, and 30-63=Severe anxiety.
measure: Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Sleep quality and disturbances during the past month were assessed with the Pittsburgh Sleep Quality Index (PSQI). The PSQI also incorporates daytime functioning into the total score. In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. The range of scores is 0-21.
measure: Change From Baseline in Menopause Specific Quality of Life (MENQOL) Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Quality of life, menopause-specific, is assessed by the Menopause Specific Quality of Life (MENQOL).
The MENQOL is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor (items 1-3), psychosocial (items 4-10), physical (items 11-26), and sexual (items 27-29). Items pertaining to a specific symptom are rated as present or not present, and if present, how bothersome on a zero (not bothersome) to six (extremely bothersome) scale. Means are computed for each subscale by dividing the sum of the domain's items by the number of items within that domain. Non-endorsement of an item is scored a "1" and endorsement a "2", plus the number of the particular rating, so that the possible score on any item ranges from 1-8. Total score also ranges from 1-8. Higher scores indicate that menopause symptoms are more bothersome.
measure: Change From Baseline in Clinical Global Impression-Fatigue (CGI-F) Scale Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Fatigue symptoms were assessed by the Clinical Global Impression-Fatigue (CGI-F) scale.The CGI-F is a single item global assessment scales to specifically evaluate symptoms of fatigue. Higher scores indicate more fatigue symptoms. The range of scores is from 0-7.
measure: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Severity of illness was assessed by the Clinical Global Impression-Severity (CGI-S) Scale. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. The range of scores is 0-7. Higher scores indicate greater severity of illness.
measure: Change From Baseline in Pain Assessment (PEG) Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Pain symptoms were assessed by the Pain Assessment (PEG). The PEG is a three-item scale assessing pain intensity and interference. A higher score indicates more pain symptoms. The range of scores is from 0 to 30.
measure: Change From Baseline in Greene Climacteric Scale (GCS) Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Menopause related symptoms were assessed using the Greene Climacteric Scale (GCS). The Greene Scale provides a brief measure of menopause symptoms. It can be used to assess changes in different symptoms, before and after menopause treatment. Three main areas are measured:
1. Psychological (items 1-11). 2. Physical (items 12-18). 3. Vasomotor (items 19, 20).
A higher score indicates that menopause symptoms are more bothersome. The range of scores is from 0 to 63.
measure: Change From Baseline in Digit Symbol Substitution Test (DSST) Score at Week 8 (Visit 5)
time frame: Baseline and Week 8 (Visit 5)
description: Processing speed, working memory, visuospatial processing and attention was assessed by the Digit Symbol Substitution Test (DSST).
The DSST test requires the examinee to transcribe a unique geometric symbol with its corresponding Arabic number. The examinee is initially shown a key containing the numbers from 1 to 9. Under each number there is a corresponding geometric symbol. The examinee is then shown a series of boxes containing numbers in the top boxes, and blank boxes below them. After a short practice trial, they are then asked to copy the corresponding geometric symbol under each number. The raw score is the number of correct items completed within the prescribed time limit. Higher scores indicate faster processing speed, working memory, and visuospatial processing and attention. The range of scores is 0-63.
arm group label: open-label vortioxetine
arm group type: Experimental
description: flexible-dose vortioxetine of 5-20 mg depending on tolerability
intervention type: Drug
intervention name: vortioxetine
description: Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.
arm group label: open-label vortioxetine
other name: Trintellix
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 62 Years
healthy volunteers: No
last name: Marlene P Freeman, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
citation: Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12.
PMID: 21486038
citation: Bromberger JT, Assmann SF, Avis NE, Schocken M, Kravitz HM, Cordal A. Persistent mood symptoms in a multiethnic community cohort of pre- and perimenopausal women. Am J Epidemiol. 2003 Aug 15;158(4):347-56. doi: 10.1093/aje/kwg155.
PMID: 12915500
citation: Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000 Dec 16;356(9247):2059-63. doi: 10.1016/S0140-6736(00)03403-6.
PMID: 11145492
citation: Pehrson AL, Cremers T, Betry C, van der Hart MG, Jorgensen L, Madsen M, Haddjeri N, Ebert B, Sanchez C. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters--a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol. 2013 Feb;23(2):133-45. doi: 10.1016/j.euroneuro.2012.04.006. Epub 2012 May 20.
PMID: 22612991
citation: Pehrson AL, Sanchez C. Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS Spectr. 2014 Apr;19(2):121-33. doi: 10.1017/S1092852913000540. Epub 2013 Aug 1.
PMID: 23903233
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Marlene P. Freeman, MD
investigator title: Associate Director, Center for Women's Mental Health
mesh term: Hot Flashes
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Vortioxetine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: lack of control group (important given that previous VMS medication trials have indicated modest placebo response rates, and it is difficult to determine whether the side effects are associated with the medication)
small sample size
point of contact: 