A Study Of Sertraline Compared With Paroxetine In The Treatment Of Panic Disorder

Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00677352
Collaborator
(none)
321
24
2
21.1
13.4
0.6

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of sertraline compared to paroxetine in patients with panic disorder.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
321 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Multicenter Study Of Sertraline Compared With Paroxetine In The Treatment Of Panic Disorder
Study Start Date :
May 1, 2008
Actual Primary Completion Date :
Jan 1, 2010
Actual Study Completion Date :
Feb 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Drug: sertraline
dosage : 25mg , 50mg , placebo; dosage form : tablet; frequency : once daily after dinner; duration : 14 weeks
Other Names:
  • Zoloft, JZoloft
  • Active Comparator: 2

    Drug: Paroxetine
    dosage : 10mg, placebo; dosage form : capsule; frequency : once daily after dinner; duration : 14 weeks
    Other Names:
  • Paxil
  • Outcome Measures

    Primary Outcome Measures

    1. Mean Change From Baseline in Panic and Agoraphobia Scale (PAS) Total Score at the End of Treatment Phase [Baseline and 12 weeks]

      Panic and Agoraphobia Scale has 13 items with a 5-point scale (range: 0 to 4). The total possible score is ranged from 0 to 52. The increasing value are considered worse outcome. The scale is grouped into 5 subscores (not including item U in total score): panic attacks ; agoraphobia/avoidance behavior ; anticipatory anxiety; disability; and health worries. Four point difference in reduction of the PAS total score has been identified as not clinically meaningful in the assessment of Panic Disorder symptomatology.

    Secondary Outcome Measures

    1. Percentage of Participants of Responder in Clinical Global Impression (CGI) - Improvement [12 weeks]

      The ratings were rated to compare with baseline by 7-point " 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse". Responder was defined as number of participants who were assessed as "very much improved" or " much improved".

    2. Mean Change From Baseline in Panic Attack at the End of Treatment Phase [Baseline and 12 weeks]

      Panic attacks were defined as having four or more of the following Diagnostic and Statistical Manual of Mental Disorders symptoms. Palpitations or increased heart rate, Sweating, Trembling or shaking, Shortness of breath or smothering sensations, Choking, Chest pain or discomfort, Nausea or upset stomach, Dizziness, unsteady feelings or faintness, Feeling unlike yourself, or detached from a situation and/or like things happening around you are strange and unreal, Fear of going crazy or doing something uncontrolled, Fear of dying, Abnormal sense, Hot flashes or chills.

    3. Mean Change From Baseline in Hamilton Anxiety Rating Scale Total Score at the End of Treatment Phase [Baseline and 12 weeks]

      The Hamilton Anxiety Rating Scale provided a 5-point intensity rating (0=None to 4=Very severe) of anxiety symptoms in 14 items. The increasing values are considered worse outcome. The total possible score is ranged from 0 to 52.

    4. Number of Participants With Summary of Adverse Events in Treatment Phase [1, 2, 4, 6, 8 10 and 12 weeks (or study discontinuation) after administration of study drug]

      Number of sparticipants with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Participants were counted only once per treatment in each row.

    5. Summary of Adverse Events in Tapering Phase [4 weeks]

      Number of subjects with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Subjects were counted only once per treatment in each row.

    6. Percentage of Participants With Deterioration in Antidepressant Discontinuation Scale During Tapering Phase [4 weeks]

      The percentage of participants divided was calcurated as follows: Devide the number of participants who had experienced new symptoms in Week 16, regardless of causal relationship with the study drug, or worsening of the severity in Week 16 compared with Week 12, by total number of participants in each treatment group.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 64 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patient who meets diagnosis of Panic Disorder (with or without Agoraphobia) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV).

    • Patients must have experienced at least 4 panic attacks within 4 weeks before screening.

    • At baseline patients with Panic Disorder of total score of 18 or higher on the Panic and Agoraphobia scale (clinician rated version).

    Exclusion Criteria:
    • Patients who concurrently have bipolar disorder, schizophrenia, delusional disorder, epilepsy, Major Depression Disorder (MDD), Obsessive Compulsive Disorder (OCD), Seasonal Affective Disorder (SAD) or General Anxiety Disorder (GAD) according to the DSM-IV criteria.

    • Patients who concurrently have depression/depressive state, anxiety disorder and generalized anxiety disorder may be included in the study if the primary diagnosis is identified to be panic disorder

    • Patients with the total score of at least 18 on the Hamilton Depression Rating Scale (HAM-D) (Items 1 to 17) at the start of Screening (Visit 1)

    • Patients who require concomitant drug therapy with psychotropic agents (including benzodiazepines) and monoamine oxidase inhibitor during the period of the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Nagoya Aichi Japan
    2 Pfizer Investigational Site Fukuoka-shi Fukuoka Japan
    3 Pfizer Investigational Site Kitakyushu-shi Fukuoka Japan
    4 Pfizer Investigational Site Kitakyusyu-shi Fukuoka Japan
    5 Pfizer Investigational Site Sapporo-Shi Hokkaido Japan
    6 Pfizer Investigational Site Sapporo Hokkaido Japan
    7 Pfizer Investigational Site Higashiibaraki-gun Ibaraki Japan
    8 Pfizer Investigational Site Fujisawa-city Kanagawa Japan
    9 Pfizer Investigational Site Sagamihara-Shi Kanagawa Japan
    10 Pfizer Investigational Site Yokohama-Shi Kanagawa Japan
    11 Pfizer Investigational Site Yokohama Kanagawa Japan
    12 Pfizer Investigational Site Kawaguchi-shi Saitama Japan
    13 Pfizer Investigational Site Saitama city Saitama Japan
    14 Pfizer Investigational Site Chiyoda-ku Tokyo Japan
    15 Pfizer Investigational Site Kita-ku Tokyo Japan
    16 Pfizer Investigational Site Minato-ku Tokyo Japan
    17 Pfizer Investigational Site Musashino Tokyo Japan
    18 Pfizer Investigational Site Nakano-Ku Tokyo Japan
    19 Pfizer Investigational Site Nakanoku Tokyo Japan
    20 Pfizer Investigational Site Setagaya-ku Tokyo Japan
    21 Pfizer Investigational Site Shinjuku-ku Tokyo Japan
    22 Pfizer Investigational Site Toshima-ku Tokyo Japan
    23 Pfizer Investigational Site Nakano-ku Yokohama Japan
    24 Pfizer Investigational Site Minato-ku Japan

    Sponsors and Collaborators

    • Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    ClinicalTrials.gov Identifier:
    NCT00677352
    Other Study ID Numbers:
    • A0501088
    First Posted:
    May 14, 2008
    Last Update Posted:
    Jan 27, 2021
    Last Verified:
    Jan 1, 2021
    Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants were screened at 34 centers in Japan.
    Pre-assignment Detail Subjects who experienced at least one panic attack that met the DSM-IV diagnostic criteria per week between the start of the washout/observation period and the start of the double-blind treatment period and who had a total score of 18 or higher on the Panic and Agoraphobia Scale at the start of the double-blind treatment period.
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Period Title: Treatment Phase
    STARTED 157 164
    COMPLETED 132 122
    NOT COMPLETED 25 42
    Period Title: Treatment Phase
    STARTED 132 122
    COMPLETED 126 112
    NOT COMPLETED 6 10

    Baseline Characteristics

    Arm/Group Title Sertraline Paroxetine Total
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks. Total of all reporting groups
    Overall Participants 157 162 319
    Age, Customized (participants) [Number]
    < 18 years
    0
    0%
    0
    0%
    0
    0%
    18 - 44 years
    119
    75.8%
    126
    77.8%
    245
    76.8%
    45 -64 years
    38
    24.2%
    36
    22.2%
    74
    23.2%
    >= 65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    113
    72%
    109
    67.3%
    222
    69.6%
    Male
    44
    28%
    53
    32.7%
    97
    30.4%

    Outcome Measures

    1. Primary Outcome
    Title Mean Change From Baseline in Panic and Agoraphobia Scale (PAS) Total Score at the End of Treatment Phase
    Description Panic and Agoraphobia Scale has 13 items with a 5-point scale (range: 0 to 4). The total possible score is ranged from 0 to 52. The increasing value are considered worse outcome. The scale is grouped into 5 subscores (not including item U in total score): panic attacks ; agoraphobia/avoidance behavior ; anticipatory anxiety; disability; and health worries. Four point difference in reduction of the PAS total score has been identified as not clinically meaningful in the assessment of Panic Disorder symptomatology.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12. Last Observation Carried Forward
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Measure Participants 127 127
    Least Squares Mean (95% Confidence Interval) [Scores on scale]
    -17.4
    -17.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertraline, Paroxetine
    Comments The two-sided 95% confidence interval (CI) of the intergroup difference (sertraline group - paroxetine group) of the mean reduction in the PAS total score at each dose during the treatment phase was calculated using an analysis of covariance (ANCOVA) model with treatment group as a factor and baseline PAS total score as a covariate.
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Sertraline was concluded to be non-inferior to paroxetine when the upper limit of the CI fell below the non-inferiority margin of 4.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants of Responder in Clinical Global Impression (CGI) - Improvement
    Description The ratings were rated to compare with baseline by 7-point " 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse". Responder was defined as number of participants who were assessed as "very much improved" or " much improved".
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12. Last Observation Carried Forward
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Measure Participants 127 127
    Number [Percentage of participants]
    83.5
    53.2%
    85.0
    52.5%
    3. Secondary Outcome
    Title Mean Change From Baseline in Panic Attack at the End of Treatment Phase
    Description Panic attacks were defined as having four or more of the following Diagnostic and Statistical Manual of Mental Disorders symptoms. Palpitations or increased heart rate, Sweating, Trembling or shaking, Shortness of breath or smothering sensations, Choking, Chest pain or discomfort, Nausea or upset stomach, Dizziness, unsteady feelings or faintness, Feeling unlike yourself, or detached from a situation and/or like things happening around you are strange and unreal, Fear of going crazy or doing something uncontrolled, Fear of dying, Abnormal sense, Hot flashes or chills.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12. Last Observation Carried Forward
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Measure Participants 127 127
    Mean (Standard Deviation) [panic attacks per week]
    -4.07
    (6.12)
    -4.59
    (7.52)
    4. Secondary Outcome
    Title Mean Change From Baseline in Hamilton Anxiety Rating Scale Total Score at the End of Treatment Phase
    Description The Hamilton Anxiety Rating Scale provided a 5-point intensity rating (0=None to 4=Very severe) of anxiety symptoms in 14 items. The increasing values are considered worse outcome. The total possible score is ranged from 0 to 52.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12. Last Observation Carried Forward
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Measure Participants 127 127
    Mean (Standard Deviation) [Scores on a scale]
    -11.35
    (10.45)
    -10.36
    (8.27)
    5. Secondary Outcome
    Title Number of Participants With Summary of Adverse Events in Treatment Phase
    Description Number of sparticipants with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Participants were counted only once per treatment in each row.
    Time Frame 1, 2, 4, 6, 8 10 and 12 weeks (or study discontinuation) after administration of study drug

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set : Subset of patients who had taken at least one dose of the study drug and who had visited the study center at least once after taking the study drug.
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Measure Participants 157 162
    Subjects with adverse events
    127
    80.9%
    134
    82.7%
    Subjects with serious adverse events
    1
    0.6%
    1
    0.6%
    Subjects with severe adverse events
    3
    1.9%
    14
    8.6%
    Subjects discontinued due to adverse events
    14
    8.9%
    23
    14.2%
    Dose reduced or temporary discontinuation
    13
    8.3%
    14
    8.6%
    6. Secondary Outcome
    Title Summary of Adverse Events in Tapering Phase
    Description Number of subjects with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Subjects were counted only once per treatment in each row.
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set : Subset of patients who had taken at least one dose of the study drug and who had visited the study center at least once after taking the study drug.
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Measure Participants 132 122
    Subjects with adverse events
    73
    46.5%
    87
    53.7%
    Subjects with serious adverse events
    1
    0.6%
    0
    0%
    Subjects with severe adverse events
    11
    7%
    16
    9.9%
    Subjects discontinued due to adverse events
    1
    0.6%
    4
    2.5%
    Dose reduced or temporary discontinuation
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Percentage of Participants With Deterioration in Antidepressant Discontinuation Scale During Tapering Phase
    Description The percentage of participants divided was calcurated as follows: Devide the number of participants who had experienced new symptoms in Week 16, regardless of causal relationship with the study drug, or worsening of the severity in Week 16 compared with Week 12, by total number of participants in each treatment group.
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    Completer Set : Subset of patients in the EES who had a PAS rating at Week 16.
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    Measure Participants 124 118
    Number [Percentage of participants]
    59.7
    38%
    76.3
    47.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertraline, Paroxetine
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0062
    Comments The p-value is not adjusted for multiple comparisons. A priori threshold for statistical significance is 0.05 (two-sided).
    Method Fisher Exact
    Comments

    Adverse Events

    Time Frame 16 weeks
    Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
    Arm/Group Title Sertraline Paroxetine
    Arm/Group Description Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
    All Cause Mortality
    Sertraline Paroxetine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Sertraline Paroxetine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/157 (1.3%) 1/162 (0.6%)
    Infections and infestations
    Enteritis infectious 0/157 (0%) 1/162 (0.6%)
    Psychiatric disorders
    Suicidal ideation 1/157 (0.6%) 0/162 (0%)
    Skin and subcutaneous tissue disorders
    Erythema multiforme 1/157 (0.6%) 0/162 (0%)
    Other (Not Including Serious) Adverse Events
    Sertraline Paroxetine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 132/157 (84.1%) 137/162 (84.6%)
    Cardiac disorders
    Palpitations 7/157 (4.5%) 10/162 (6.2%)
    Tachycardia 5/157 (3.2%) 13/162 (8%)
    Ear and labyrinth disorders
    Tinnitus 1/157 (0.6%) 10/162 (6.2%)
    Vertigo 7/157 (4.5%) 21/162 (13%)
    Gastrointestinal disorders
    Abdominal discomfort 7/157 (4.5%) 6/162 (3.7%)
    Abdominal pain upper 11/157 (7%) 8/162 (4.9%)
    Constipation 7/157 (4.5%) 23/162 (14.2%)
    Diarrhoea 37/157 (23.6%) 29/162 (17.9%)
    Dry mouth 15/157 (9.6%) 10/162 (6.2%)
    Nausea 43/157 (27.4%) 66/162 (40.7%)
    Stomatitis 5/157 (3.2%) 1/162 (0.6%)
    Vomiting 7/157 (4.5%) 13/162 (8%)
    General disorders
    Asthenia 7/157 (4.5%) 15/162 (9.3%)
    Chills 9/157 (5.7%) 16/162 (9.9%)
    Fatigue 12/157 (7.6%) 17/162 (10.5%)
    Feeling jittery 6/157 (3.8%) 15/162 (9.3%)
    Irritability 8/157 (5.1%) 22/162 (13.6%)
    Malaise 12/157 (7.6%) 17/162 (10.5%)
    Thirst 6/157 (3.8%) 7/162 (4.3%)
    Infections and infestations
    Nasopharyngitis 37/157 (23.6%) 35/162 (21.6%)
    Metabolism and nutrition disorders
    Decreased appetite 6/157 (3.8%) 9/162 (5.6%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal stiffness 7/157 (4.5%) 1/162 (0.6%)
    Myalgia 7/157 (4.5%) 16/162 (9.9%)
    Nervous system disorders
    Disturbance in attention 9/157 (5.7%) 19/162 (11.7%)
    Dizziness 42/157 (26.8%) 61/162 (37.7%)
    Headache 20/157 (12.7%) 47/162 (29%)
    Hypoaesthesia 5/157 (3.2%) 9/162 (5.6%)
    Myoclonus 4/157 (2.5%) 6/162 (3.7%)
    Paraesthesia 4/157 (2.5%) 11/162 (6.8%)
    Somnolence 34/157 (21.7%) 62/162 (38.3%)
    Tremor 6/157 (3.8%) 19/162 (11.7%)
    Psychiatric disorders
    Abnormal dreams 4/157 (2.5%) 11/162 (6.8%)
    Anxiety 16/157 (10.2%) 24/162 (14.8%)
    Depression 9/157 (5.7%) 14/162 (8.6%)
    Insomnia 19/157 (12.1%) 30/162 (18.5%)
    Mood altered 8/157 (5.1%) 15/162 (9.3%)
    Panic disorder 2/157 (1.3%) 6/162 (3.7%)
    Respiratory, thoracic and mediastinal disorders
    Yawning 3/157 (1.9%) 8/162 (4.9%)
    Skin and subcutaneous tissue disorders
    Hyperhidrosis 16/157 (10.2%) 18/162 (11.1%)
    Urticaria 5/157 (3.2%) 2/162 (1.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    ClinicalTrials.gov Identifier:
    NCT00677352
    Other Study ID Numbers:
    • A0501088
    First Posted:
    May 14, 2008
    Last Update Posted:
    Jan 27, 2021
    Last Verified:
    Jan 1, 2021