Trial Outcomes & Findings for Study Evaluating Desvenlafaxine Succinate Sustained Release In Adults With Major Depressive Disorder (NCT NCT00863798)

Last Updated: 2011-05-06

Results Overview

HAM-D17: a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

682 participants

Primary outcome timeframe

Baseline and Week 8 (or ET)

Results posted on

2011-05-06

Participant Flow

A total of 898 potential participants were screened for this study. 804 participants were enrolled and received single-blind placebo during the screening period prior to randomization.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Overall Study STARTED	227	228	227
Overall Study Treated	223	226	224
Overall Study COMPLETED	195	198	202
Overall Study NOT COMPLETED	32	30	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Overall Study Adverse Event	5	2	4
Overall Study Participant failed to return	2	1	0
Overall Study Investigator request	1	2	1
Overall Study Lack of Efficacy	4	3	6
Overall Study Lost to Follow-up	6	9	5
Overall Study Other	2	3	1
Overall Study Protocol Violation	0	1	1
Overall Study Withdrawal by Subject	8	7	4
Overall Study Randomized not treated	4	2	3

Baseline Characteristics

Study Evaluating Desvenlafaxine Succinate Sustained Release In Adults With Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.	Total n=673 Participants Total of all reporting groups
Age Continuous	41.75 Years STANDARD_DEVIATION 12.85 • n=5 Participants	41.01 Years STANDARD_DEVIATION 13.75 • n=7 Participants	42.47 Years STANDARD_DEVIATION 13.47 • n=5 Participants	41.74 Years STANDARD_DEVIATION 13.36 • n=4 Participants
Sex: Female, Male Female	139 Participants n=5 Participants	135 Participants n=7 Participants	135 Participants n=5 Participants	409 Participants n=4 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	91 Participants n=7 Participants	89 Participants n=5 Participants	264 Participants n=4 Participants
Hamilton Psychiatric Scale for Depression-17 item HAM-D17) total score	23.23 Units on a scale STANDARD_DEVIATION 2.63 • n=5 Participants	22.83 Units on a scale STANDARD_DEVIATION 2.26 • n=7 Participants	23.12 Units on a scale STANDARD_DEVIATION 2.62 • n=5 Participants	23.06 Units on a scale STANDARD_DEVIATION 2.51 • n=4 Participants
Clinical Global Impressions Scale-Severity of Illness (CGI-S) Score	4.14 Units on a scale STANDARD_DEVIATION 0.35 • n=5 Participants	4.14 Units on a scale STANDARD_DEVIATION 0.34 • n=7 Participants	4.16 Units on a scale STANDARD_DEVIATION 0.39 • n=5 Participants	4.14 Units on a scale STANDARD_DEVIATION 0.36 • n=4 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) total score	28.33 Units on a scale STANDARD_DEVIATION 4.71 • n=5 Participants	27.59 Units on a scale STANDARD_DEVIATION 4.49 • n=7 Participants	28.44 Units on a scale STANDARD_DEVIATION 4.83 • n=5 Participants	28.12 Units on a scale STANDARD_DEVIATION 4.69 • n=4 Participants
HAM-D6 total score	12.72 Units on a scale STANDARD_DEVIATION 1.51 • n=5 Participants	12.77 Units on a scale STANDARD_DEVIATION 1.41 • n=7 Participants	12.63 Units on a scale STANDARD_DEVIATION 1.49 • n=5 Participants	12.71 Units on a scale STANDARD_DEVIATION 1.47 • n=4 Participants
Sheehan Disability Scale (SDS) Total Score	16.88 Units on a scale STANDARD_DEVIATION 8.25 • n=5 Participants	16.42 Units on a scale STANDARD_DEVIATION 8.37 • n=7 Participants	17.06 Units on a scale STANDARD_DEVIATION 7.73 • n=5 Participants	16.78 Units on a scale STANDARD_DEVIATION 8.12 • n=4 Participants
World Health Organization 5-Item Well-Being Index (WHO-5)	7.39 Units on a scale STANDARD_DEVIATION 4.80 • n=5 Participants	7.47 Units on a scale STANDARD_DEVIATION 4.86 • n=7 Participants	7.06 Units on a scale STANDARD_DEVIATION 4.26 • n=5 Participants	7.31 Units on a scale STANDARD_DEVIATION 4.65 • n=4 Participants
Participants with Sexual dysfunction	58.8 Percentage of Participants n=5 Participants	61.3 Percentage of Participants n=7 Participants	65.8 Percentage of Participants n=5 Participants	185.9 Percentage of Participants n=4 Participants
Participants with Columbia Suicide-Severity Rating Scale (C-SSRS) total score Completed Suicide	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Participants with Columbia Suicide-Severity Rating Scale (C-SSRS) total score Suicide Attempt	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Participants with Columbia Suicide-Severity Rating Scale (C-SSRS) total score Preparatory acts toward imminent suicidal behavior	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Participants with Columbia Suicide-Severity Rating Scale (C-SSRS) total score Suicidal ideation	37 Participants n=5 Participants	31 Participants n=7 Participants	29 Participants n=5 Participants	97 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8 (or ET)

Population: Intent-To-Treat (ITT) Population:all randomly assigned participants with baseline primary efficacy evaluation, had taken at least 1 dose of double-blind drug and 1 primary efficacy evaluation after first dose of double-blind drug. If participant had missing value at any visit, last observation carried forward (LOCF) method of imputation was used.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Change From Baseline in HAM-D17 Total Score at Final On-therapy (FOT) Evaluation (Week 8 or ET)	-8.42 Units on a scale Standard Error 0.45	-9.28 Units on a scale Standard Error 0.45	-8.92 Units on a scale Standard Error 0.45

SECONDARY outcome

Timeframe: Week 8 (or ET)

Population: ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study drug, and had at least 1 primary efficacy evaluation after first dose of double-blind study drug. If participant had a missing value at any visit, LOCF method of imputation was used.

CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) 1=Very much improved	49 Participants	50 Participants	55 Participants
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) 2=Much improved	54 Participants	75 Participants	53 Participants
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) 3=Minimally improved	51 Participants	51 Participants	64 Participants
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) 4=No change	61 Participants	46 Participants	49 Participants
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) 5=Minimally worse	5 Participants	4 Participants	3 Participants
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) 6=Much worse	3 Participants	0 Participants	0 Participants
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) 7=Very much worse	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 8 (or ET )

CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Change From Baseline in Mean CGI-S Score at FOT Evaluation (Week 8 or ET)	-1.08 Units on a scale Standard Error 0.07	-1.23 Units on a scale Standard Error 0.07	-1.11 Units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline and Week 8 (or ET)

MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=224 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=222 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Change From Baseline in MADRS Total Score at FOT Evaluation (Week 8 or ET)	-9.87 Units on a scale Standard Error 0.63	-11.28 Units on a scale Standard Error 0.63	-10.76 Units on a scale Standard Error 0.63

SECONDARY outcome

Timeframe: Baseline and Week 8 (or ET )

HAM-D6: a standardized, clinician-administered rating scale that assesses 6 items characteristically associated with major depression and is a subset of HAM-D17. HAM-D6 score ranges from 0-22. 0=none/absent and 22=most severe.The scale uses HAM-D17 items: 1, 2, 7, 8, 10 and 13. Item 13 is scored 0-2 and all others are scored 0-4.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Change From Baseline in HAM-D6 Total Score at FOT Evaluation (Week 8 or ET)	-4.75 Units on a scale Standard Error 0.27	-5.49 Units on a scale Standard Error 0.27	-5.19 Units on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Week 8 (or ET)

A HAM-D17 responder was defined as a participant with a 50% or greater decrease from baseline in HAM-D17 score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Number of Participants With a Response on the HAM-D17 at FOT Evaluation (Week 8 or ET)	85 Participants	100 Participants	91 Participants

SECONDARY outcome

Timeframe: Week 8 (or ET)

Remission was defined as a HAM-D17 score of less than or equal to 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Number of Participants in Remission Based on the HAM-D17 at FOT Evaluation (Week 8 or ET)	42 Participants	52 Participants	39 Participants

SECONDARY outcome

Timeframe: Week 8 (or ET)

A MADRS responder was defined as a participant with a 50% or greater decrease from baseline in MADRS score. It measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=224 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=222 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Number of Participants With a Response on the MADRS Score at FOT Evaluation (Week 8 or ET)	84 Participants	95 Participants	90 Participants

SECONDARY outcome

Timeframe: Week 8 (or ET)

CGI-I responder was defined as a participant with a score of 1 (very much improved) or 2 (much improved) on the CGI-I. CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Number of Participants With a Response on the CGI-I Score at FOT Evaluation (Week 8 or ET)	103 Participants	125 Participants	108 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2, 4 and 8 (or ET)

Population: PK population; data was insufficient examine the effect of demographic variables on the PK of desvenlafaxine. Parameter values were calculated for variables altering CL/F, AUC and V/F. Population parameters from nonlinear mixed effects modeling were not summarized as descriptive statistics.

Relationship of demographic variables (age, gender, food, race, creatinine, aspartate aminotransaminase, alanine transaminase, bilirubin and concomitant medications) were examined by fitting measured DVS plasma concentrations to a 1 compartment model with first order absorption. Demographic variables were examined for clearance (CL/F), volume of distribution (V/F), Steady Area under Curve (AUC) using nonlinear mixed effects modeling. Final parameter estimates for demographic factors effecting CL/F, V/F and AUC were determined.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 8 (or ET)

Population: ITT Population included all randomly assigned participants who had baseline primary efficacy evaluation,had taken at least 1 dose of double-blind study drug,had at least 1 primary efficacy evaluation after first dose of double-blind drug.'n' is participants who received drug and were evaluated for measure at timepoint for each group respectively.

SDS: a self-administered tools that measures functional impairment in 3 domains: Work/School, Social Life, and Family Life/Home Responsibilities. The participant rates the extent to which each of these domains is impaired by his/her symptoms using a 10 point visual analog scale: (0=not at all impaired, 10=extremely impaired) for a total maximum score of 30.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) Total Score (n=220,223,219)	-2.63 Units on a scale Standard Error 0.48	-4.09 Units on a scale Standard Error 0.48	-3.78 Units on a scale Standard Error 0.49
Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) Work/Studies Component(n=220,223,219)	-0.61 Units on a scale Standard Error 0.17	-1.10 Units on a scale Standard Error 0.17	-1.14 Units on a scale Standard Error 0.17
Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) Social Life and Leisure Activities(n=222,224,221)	-1.08 Units on a scale Standard Error 0.18	-1.58 Units on a scale Standard Error 0.17	-1.36 Units on a scale Standard Error 0.18
Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) Family Life/Home Responsibilities (n=222,224,221)	-0.98 Units on a scale Standard Error 0.17	-1.43 Units on a scale Standard Error 0.17	-1.20 Units on a scale Standard Error 0.17

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 8 (or ET)

WHO-5 evaluates positive psychological well-being. WHO-5 consists of 5 questions and each is rated on a 6-point scale. The total score ranges from 0 to 25 (0= worst possible quality of life; 25=best possible quality of life).

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=224 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=221 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Change From Baseline in WHO-5 Total Score at FOT Evaluation (Week 8 or ET)	2.96 Units on a scale Standard Error 0.36	4.51 Units on a scale Standard Error 0.35	3.73 Units on a scale Standard Error 0.36

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 8 (or ET)

Population: The safety population included all participants randomly assigned to treatment who had taken at least 1 dose of double-blind study drug.

ASEX scale includes 5 questions that evaluate sexual function exclusively during the week prior to completion in the following areas: libido, excitability and ability to reach orgasm. Sexual dysfunction=an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items. Participants who have had no sexual activity during the prior week were instructed to not complete questions 3 through 5.

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=222 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=220 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Percentage of Participants With Sexual Dysfunction at FOT Evaluation (Week 8 or ET)	52.0 Percentage of Participants	48.6 Percentage of Participants	59.5 Percentage of Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 8 (or ET)

Population: The safety population included all participants randomly assigned to treatment who had taken at least 1 dose of double-blind study drug.

C-SSRS mapped into C-CASA(1-7) to assess whether participant:completed suicide(1),suicide attempt(2)(response of "Yes" on "Actual Attempt"),preparatory acts toward imminent suicidal behavior (3)("Yes" on "Preparatory Acts or Behavior"),suicidal ideation (4)("Yes" on "Wish to be dead","Non-Specific Active Suicidal Thoughts","Active Suicidal Ideation with methods without Intent to Act or Some Intent to Act,without Specific Plan or with Specific Plan and Intent),any suicidal behavior or ideation,self-injurious behaviour(7)("Yes" on "Has subject engaged in Non-suicidal Self-Injurious Behavior").

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) Completed suicide	0 Participants	0 Participants	0 Participants
Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) Suicide attempt	0 Participants	1 Participants	0 Participants
Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) Preparatory acts toward imminent suicidal behavior	0 Participants	0 Participants	1 Participants
Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) Suicidal ideation	56 Participants	43 Participants	45 Participants
Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) Any suicidal behavior and/or ideation	56 Participants	43 Participants	45 Participants
Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) Self-injurious behavior, no suicidal intent	1 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 8 to 10 (or ET)

Population: Analysis included completers for exposure (those whose exposure duration was at least 53 days) among safety population. 'n' is participants who received drug and were evaluated for measure at timepoint for each group respectively.

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of new symptoms and old (but worse) symptoms that appeared during tapering of the test article. A higher score indicates more symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 Participants Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 Participants DVS SR 50 mg daily until Day 56 (Week 8) or ET.
Discontinuation-Emergent Signs and Symptoms (DESS) Week 8 (or ET) (n=190,194,191)	0.72 Units on a scale Standard Deviation 1.81	0.80 Units on a scale Standard Deviation 1.78	0.83 Units on a scale Standard Deviation 2.05
Discontinuation-Emergent Signs and Symptoms (DESS) Week 9 ( or ET + 1 week) (n=178,185,186)	1.26 Units on a scale Standard Deviation 2.78	1.08 Units on a scale Standard Deviation 2.31	1.98 Units on a scale Standard Deviation 3.29
Discontinuation-Emergent Signs and Symptoms (DESS) Week 10 (or ET + 2 weeks (n=170,182,182)	0.90 Units on a scale Standard Deviation 2.30	0.91 Units on a scale Standard Deviation 2.24	1.07 Units on a scale Standard Deviation 2.50

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 166 other events

Deaths: 0 deaths

DVS SR 10 mg

Serious events: 1 serious events

Other events: 168 other events

Deaths: 0 deaths

DVS SR 50 mg

Serious events: 1 serious events

Other events: 170 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=223 participants at risk Matching placebo tablets daily until Day 56 (Week 8) or early termination (ET).	DVS SR 10 mg n=226 participants at risk Desvenlafaxine Succinate Sustained Release (DVS SR) 10 mg daily until Day 56 (Week 8) or ET.	DVS SR 50 mg n=224 participants at risk DVS SR 50 mg daily until Day 56 (Week 8) or ET.
General disorders Non-cardiac chest pain	0.45% 1/223 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.	0.00% 0/226 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.	0.00% 0/224 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.
Infections and infestations Appendicitis	0.45% 1/223 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.	0.00% 0/226 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.	0.00% 0/224 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.
Infections and infestations Scrotal abscess	0.45% 1/223 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.	0.00% 0/226 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.	0.00% 0/224 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.
Renal and urinary disorders Urinary retention	0.00% 0/223 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.	0.44% 1/226 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.	0.00% 0/224 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.
Reproductive system and breast disorders Epididymitis	0.45% 1/223 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.	0.00% 0/226 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.	0.00% 0/224 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/223 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.	0.00% 0/226 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.	0.45% 1/224 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.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER