<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 March 05, 2021</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/show/NCT00000378</url>
</required_header>
<id_info>
<org_study_id>#3105</org_study_id>
<secondary_id>R01MH055716</secondary_id>
<nct_id>NCT00000378</nct_id>
</id_info>
<brief_title>Antidepressant Treatment of Melancholia in Late Life</brief_title>
<official_title>Antidepressant Treatment of Melancholia in Late :Ife</official_title>
<sponsors>
<lead_sponsor>
<agency>New York State Psychiatric Institute</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Institute of Mental Health (NIMH)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>New York State Psychiatric Institute</source>
<oversight_info>
<has_dmc>No</has_dmc>
</oversight_info>
<brief_summary>
<textblock>
The purpose of this study is to compare the safety and effectiveness of a select serotonin
re-uptake inhibitor (SSRI, sertraline) and a tricyclic antidepressant (TCA, nortriptyline) in
outpatients over the age of 60 who have major depression.

SSRIs are effective in the treatment of major depression. However, there is also evidence
that SSRIs may be significantly less effective than TCAs for patients with late-life major
depression with melancholia. Since SSRIs seem to be easier to take than TCAs and are more
widely prescribed, it is important to determine which of these types of antidepressants works
best to treat these patients.

Patients will be assigned randomly to receive either sertraline (a SSRI) or nortriptyline (a
TCA) for 12 weeks. Patients will be monitored for symptoms, side effects, and quality of
life. If a patient responds to treatment, he/she will participate in a 6-month continuation
phase in which he/she will continue to receive the same medication.

An individual may be eligible for this study if he/she:

Has unipolar major depression (with some exceptions) and is over 60 years old.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
To compare the efficacy and safety of a select serotonin re-uptake inhibitor (SSRI,
sertraline) and a tricyclic antidepressant (TCA, nortriptyline) in outpatients over the age
of 60 who meet Diagnostic and Statistical Manuel-IV criteria for unipolar major depression,
excluding patients who meet criteria for psychotic or atypical subtype. To test the
hypothesis that medication condition interacts with diagnostic subtype (melancholic vs
non-melancholic) in determining antidepressant response. To examine the roles of symptom
severity and alternative diagnostic subtyping in contributing to this pattern.

SSRIs are effective in the treatment of major depression. However, there is also evidence
that SSRIs may be significantly less effective than TCAs for depressed patients with
melancholia. This issue is of particular concern in late-life major depression. SSRIs have
important safety advantages with respect to overdose and a benign cardiovascular profile.
Furthermore, the SSRIs do not have significant anticholinergic effects, and appear to be
better tolerated than the TCAs. Perhaps most important, the SSRIs currently are prescribed
widely as the medication treatment of first choice for major depression in late life.
Therefore, if it were determined that SSRIs are considerably less effective than TCAs in the
treatment of melancholia in the elderly, there would be significant ramifications for
clinical practice.

Randomization to sertraline (a SSRI) or nortriptyline (a TCA) is stratified by the presence
or absence of melancholia. Outcome measures for the 12-week acute phase include clinician and
patient ratings of symptoms, side effects, and an evaluation of the health-related quality of
life (HRQOL). At the end of the acute treatment phase, patients who meet criteria for
clinical response participate in a 6-month continuation phase.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date>July 1997</start_date>
<completion_date type="Actual">June 2002</completion_date>
<primary_completion_date type="Actual">June 2002</primary_completion_date>
<phase>Phase 4</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>HAMILTON Rating Scale for DEPRESSION Range</measure>
<time_frame>BASELINE COMPARED TO 12 WEEK MEASUREMENT</time_frame>
<description>Hamilton scale range 0-40, values below 7 are considered normal. the higher the number the more severe the depression weekly assessments, The primary outcome is a comparison of the baseline Hamilton to the 12 week measurement</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">110</enrollment>
<condition>Depression</condition>
<condition>Melancholia</condition>
<arm_group>
<arm_group_label>sertaline</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>patients randomized to sertraline 12 week trial does up to 200mgs</description>
</arm_group>
<arm_group>
<arm_group_label>nortriptyline</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>patients randomized to nortriptyline dose adjusted to therapeutic level</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Sertraline</intervention_name>
<description>12 week trial dose up to 200mgs</description>
<arm_group_label>sertaline</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Nortriptyline</intervention_name>
<description>12 week trial dose adjusted to therapeutic level</description>
<arm_group_label>nortriptyline</arm_group_label>
<other_name>nortiptyline</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

-

Patients must have:

Unipolar major depression (per Diagnostic and Statistical Manuel-IV criteria) with or
without melancholia.

Exclusion Criteria:

-

Patients with the following symptoms or conditions are excluded:

Psychotic or atypical subtype of unipolar major depression.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>60 Years</minimum_age>
<maximum_age>95 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Steven P. Roose, MD</last_name>
<role>Principal Investigator</role>
<affiliation>New York State Psychiatric Institute</affiliation>
</overall_official>
<location>
<facility>
<name>1051 Riverside Drive</name>
<address>
<city>New York</city>
<state>New York</state>
<zip>10032</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>September 2008</verification_date>
<study_first_submitted>November 2, 1999</study_first_submitted>
<study_first_submitted_qc>November 2, 1999</study_first_submitted_qc>
<study_first_posted type="Estimate">November 3, 1999</study_first_posted>
<results_first_submitted>April 2, 2015</results_first_submitted>
<results_first_submitted_qc>April 17, 2015</results_first_submitted_qc>
<results_first_posted type="Estimate">April 21, 2015</results_first_posted>
<last_update_submitted>October 6, 2015</last_update_submitted>
<last_update_submitted_qc>October 6, 2015</last_update_submitted_qc>
<last_update_posted type="Estimate">October 7, 2015</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Aged</keyword>
<keyword>Antidepressive Agents, Tricyclic</keyword>
<keyword>Depression</keyword>
<keyword>Female</keyword>
<keyword>Human</keyword>
<keyword>Male</keyword>
<keyword>Middle Age</keyword>
<keyword>Nortriptyline</keyword>
<keyword>Sertraline</keyword>
<keyword>Serotonin Uptake Inhibitors</keyword>
<keyword>Antidepressive Agents, Tricyclic -- *therapeutic use</keyword>
<keyword>Antidepressive Agents, Tricyclic -- adverse effects</keyword>
<keyword>Depression -- *drug therapy</keyword>
<keyword>Nortriptyline -- *therapeutic use</keyword>
<keyword>Nortriptyline -- adverse effects</keyword>
<keyword>Sertraline -- *therapeutic use</keyword>
<keyword>Sertraline -- adverse effects</keyword>
<keyword>Serotonin Uptake Inhibitors -- *therapeutic use</keyword>
<keyword>Serotonin Uptake Inhibitors -- adverse effects</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<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>Sertraline</mesh_term>
<mesh_term>Nortriptyline</mesh_term>
</intervention_browse>
<clinical_results>
<participant_flow>
<group_list>
<group group_id="P1">
<title>Sertaline</title>
<description>patients randomized to sertraline 12 week trial does up to 200mgs
Sertraline: 12 week trial dose up to 200mgs</description>
</group>
<group group_id="P2">
<title>Nortriptyline</title>
<description>patients randomized to nortriptyline dose adjusted to therapeutic level
Nortriptyline: 12 week trial dose adjusted to therapeutic level</description>
</group>
</group_list>
<period_list>
<period>
<title>Overall Study</title>
<milestone_list>
<milestone>
<title>STARTED</title>
<participants_list>
<participants group_id="P1" count="58"/>
<participants group_id="P2" count="52"/>
</participants_list>
</milestone>
<milestone>
<title>COMPLETED</title>
<participants_list>
<participants group_id="P1" count="42"/>
<participants group_id="P2" count="38"/>
</participants_list>
</milestone>
<milestone>
<title>NOT COMPLETED</title>
<participants_list>
<participants group_id="P1" count="16"/>
<participants group_id="P2" count="14"/>
</participants_list>
</milestone>
</milestone_list>
<drop_withdraw_reason_list>
<drop_withdraw_reason>
<title>Lack of Efficacy</title>
<participants_list>
<participants group_id="P1" count="16"/>
<participants group_id="P2" count="14"/>
</participants_list>
</drop_withdraw_reason>
</drop_withdraw_reason_list>
</period>
</period_list>
</participant_flow>
<baseline>
<group_list>
<group group_id="B1">
<title>Sertaline</title>
<description>patients randomized to sertraline 12 week trial does up to 200mgs
Sertraline: 12 week trial dose up to 200mgs</description>
</group>
<group group_id="B2">
<title>Nortriptyline</title>
<description>patients randomized to nortriptyline dose adjusted to therapeutic level
Nortriptyline: 12 week trial dose adjusted to therapeutic level</description>
</group>
<group group_id="B3">
<title>Total</title>
<description>Total of all reporting groups</description>
</group>
</group_list>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Overall</scope>
<count_list>
<count group_id="B1" value="58"/>
<count group_id="B2" value="52"/>
<count group_id="B3" value="110"/>
</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><=18 years</title>
<measurement_list>
<measurement group_id="B1" value="0"/>
<measurement group_id="B2" value="0"/>
<measurement group_id="B3" value="0"/>
</measurement_list>
</category>
<category>
<title>Between 18 and 65 years</title>
<measurement_list>
<measurement group_id="B1" value="8"/>
<measurement group_id="B2" value="4"/>
<measurement group_id="B3" value="12"/>
</measurement_list>
</category>
<category>
<title>>=65 years</title>
<measurement_list>
<measurement group_id="B1" value="50"/>
<measurement group_id="B2" value="48"/>
<measurement group_id="B3" value="98"/>
</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="34"/>
<measurement group_id="B2" value="30"/>
<measurement group_id="B3" value="64"/>
</measurement_list>
</category>
<category>
<title>Male</title>
<measurement_list>
<measurement group_id="B1" value="24"/>
<measurement group_id="B2" value="22"/>
<measurement group_id="B3" value="46"/>
</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="58"/>
<measurement group_id="B2" value="52"/>
<measurement group_id="B3" value="110"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</measure_list>
</baseline>
<outcome_list>
<outcome>
<type>Primary</type>
<title>HAMILTON Rating Scale for DEPRESSION Range</title>
<description>Hamilton scale range 0-40, values below 7 are considered normal. the higher the number the more severe the depression weekly assessments, The primary outcome is a comparison of the baseline Hamilton to the 12 week measurement</description>
<time_frame>BASELINE COMPARED TO 12 WEEK MEASUREMENT</time_frame>
<population>intent to treat analysis</population>
<group_list>
<group group_id="O1">
<title>Sertaline</title>
<description>patients randomized to sertraline 12 week trial does up to 200mgs
Sertraline: 12 week trial dose up to 200mgs</description>
</group>
<group group_id="O2">
<title>Nortriptyline</title>
<description>patients randomized to nortriptyline dose adjusted to therapeutic level
Nortriptyline: 12 week trial dose adjusted to therapeutic level</description>
</group>
</group_list>
<measure>
<title>HAMILTON Rating Scale for DEPRESSION Range</title>
<description>Hamilton scale range 0-40, values below 7 are considered normal. the higher the number the more severe the depression weekly assessments, The primary outcome is a comparison of the baseline Hamilton to the 12 week measurement</description>
<population>intent to treat analysis</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="58"/>
<count group_id="O2" value="52"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<title>BASELINE</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="27.3" spread="6.6"/>
<measurement group_id="O2" value="27.1" spread="4.4"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>12 WEEK DATA</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="10.7" spread="8.3"/>
<measurement group_id="O2" value="8.4" spread="7.7"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<analysis_list>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O2</group_id>
</group_id_list>
<groups_desc>logistic regression and mixed effects model</groups_desc>
<non_inferiority_type>Superiority or Other</non_inferiority_type>
<p_value><0.05</p_value>
<p_value_desc>actual calculation</p_value_desc>
<method>Regression, Logistic</method>
</analysis>
</analysis_list>
</outcome>
</outcome_list>
<reported_events>
<group_list>
<group group_id="E1">
<title>Sertaline</title>
<description>patients randomized to sertraline 12 week trial does up to 200mgs
Sertraline: 12 week trial dose up to 200mgs</description>
</group>
<group group_id="E2">
<title>Nortriptyline</title>
<description>patients randomized to nortriptyline dose adjusted to therapeutic level
Nortriptyline: 12 week trial dose adjusted to therapeutic level</description>
</group>
</group_list>
<serious_events>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, serious adverse events</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="58"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
</event>
</event_list>
</category>
</category_list>
</serious_events>
<other_events>
<frequency_threshold>5</frequency_threshold>
<default_assessment>Systematic Assessment</default_assessment>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, other adverse events</sub_title>
<counts group_id="E1" subjects_affected="2" subjects_at_risk="58"/>
<counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
</event>
</event_list>
</category>
<category>
<title>Cardiac disorders</title>
<event_list>
<event>
<sub_title>orthostatic hypotension</sub_title>
<counts group_id="E1" subjects_affected="2" subjects_at_risk="58"/>
<counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
</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>
<point_of_contact>
<name_or_title>Steven Roose MD</name_or_title>
<organization>New York State Psychiatric Institute</organization>
<phone>646-774-8661</phone>
<email>spr2@columbia.edu</email>
</point_of_contact>
</clinical_results>
</clinical_study>
