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Effectiveness of Long-Term Versus Short-Term Treatment of Generalized Anxiety Disorder With Venlafaxine XR

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ClinicalTrials.gov Identifier: NCT00183274
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : November 30, 2016
Last Update Posted : January 16, 2017
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Karl Rickels, University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Anxiety Disorders
Interventions Drug: Venlafaxine XR
Drug: Placebo
Enrollment 268
Recruitment Details Most patients (n=239) were recruited and seen by Penn research psychiatrists in 4 primary care practices; others (n=95) responded to media advertising (radio & print ads) at the central clinic at the University of Pennsylvania
Pre-assignment Details 7-day washout period of any psychoactive medication;other antidepressants and herbal products. Subject on certain medications, such as monamine oxidase inhibitor, investigational and antipsychotic drugs had to be off these medications for at least 30 days.
Arm/Group Title Phase 1: Open-Label Phase 2: Double-Blind Venlafaxine XR Phase 2: Double-Blind Placebo Phase 3: Double-Blind Relapse Phase (Drug After Drug) Phase 3: Double-Blind Relapse Phase (Placebo After Drug) Phase 3: Double-Blind Relapse Phase (Placebo After Placebo)
Hide Arm/Group Description Patients received 75mg - 225 mg of open-label venlafaxine XR for 6 months. Responders to 6 months of open-label venlafaxine XR treatment were randomized to double-blind treatment in 60:40 ratio of drug to placebo Responders to 6 months of open-label venlafaxine XR treatment were randomized to double-blind treatment in a 60:40 ratio of drug to placebo Patients administered venlafaxine XR in phase 2 continued to take the drug during phase 3 Patients administered venlafaxine XR in Phase 2 were given a placebo in Phase 3 Patients administered placebo in Phase 2 continued to take placebo during Phase 3
Period Title: Phase 1: Open-Label
Started 268 0 0 0 0 0
Completed 158 [1] 0 0 0 0 0
Not Completed 110 0 0 0 0 0
Reason Not Completed
Adverse Event             31             0             0             0             0             0
Lack of Efficacy             13             0             0             0             0             0
Protocol Violation             11             0             0             0             0             0
Withdrawal by Subject             13             0             0             0             0             0
Lost to Follow-up             33             0             0             0             0             0
Other             9             0             0             0             0             0
[1]
110 dropouts during phase 1
Period Title: Phase 2: Double-Blind
Started 0 [1] 82 [2] 54 [2] 0 0 0
Completed 0 56 [3] 11 [4] 0 0 0
Not Completed 0 26 43 0 0 0
Reason Not Completed
Relapsed             0             8             29             0             0             0
Withdrawal by Subject             0             18             14             0             0             0
[1]
This phase ended after 6 months. There were no longer participants in this phase.
[2]
22 did not enter phase 2 due to lack of efficacy and withdrawal of consent
[3]
8 lost to relapse, 18 lost to dropout
[4]
29 lost to relapse, 14 lost to dropout
Period Title: Phase 3: Double-Blind
Started 0 0 [1] 0 [1] 15 [2] 34 [2] 10 [2]
Completed 0 0 0 13 [3] 14 [4] 6 [5]
Not Completed 0 0 0 2 20 4
Reason Not Completed
Withdrawal by Subject             0             0             0             1             9             2
Relapsed             0             0             0             1             11             2
[1]
Phase 2 ended at the end of 12 months of study.
[2]
8 completed Phase 2 but did not enter phase 3
[3]
1 lost to relapse and 1 lost to dropout
[4]
11 lost to relapse and 9 lost to dropout
[5]
2 lost to relapse and 2 lost to dropout
Arm/Group Title Venlafaxine XR
Hide Arm/Group Description

Venlafaxine XR flexible dose of 75 - 225 mg/d

Venlafaxine XR : All participants will take venlafaxine for 6 months. After this initial 6 months, participants who are not randomized to placebo will continue to take venlafaxine.

Overall Number of Baseline Participants 334
Hide Baseline Analysis Population Description
334 participants were consented, but 64 withdrew consent and 2 deviated from protocol, resulting in 268 participants who entered the initial Phase 1.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 334 participants
<=18 years
4
   1.2%
Between 18 and 65 years
280
  83.8%
>=65 years
50
  15.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 334 participants
46.11  (16.14)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 334 participants
Female
210
  62.9%
Male
124
  37.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 334 participants
334
1.Primary Outcome
Title Hamilton Rating Scale for Anxiety
Hide Description

Hamilton Rating Scale for Anxiety - The assessment of anxiety states by rating

Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0–56, where <17 indicates mild severity, 18–24 mild to moderate severity and 25–30 moderate to severe.

Time Frame Measured at Months 6 (Open Label), 12 (Double-Blind), and 18 (Double-Blind Relapse)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analytic method was time-to-relapse analyses estimated using a discrete-time Cox proportional hazards model.
Arm/Group Title Open-Label: Venlafaxine XR Double-Blind Venlafaxine XR Double-Blind Placebo Double-Blind Relapse Drug After Drug Double-Blind Relapse Placebo After Drug Double-Blind Placebo After Placebo
Hide Arm/Group Description:
A 6-month open label administration of flexible dose Venlafaxine XR that occurred between months 1 - 6 of study.
A 6-month double-blind administration of Venlafaxine XR that occurred between months 7 - 12.
A 6-month double-blind administration of placebo that occurred between months 7 - 12.
A 6-month double-blind administration of Venlafaxine XR that occurred between months 13 - 18.
A 6-month double-blind administration of placebo that occurred between months 13 - 18.
A 6-month double-blind administration of placebo that occurred between months 13 - 18.
Overall Number of Participants Analyzed 268 82 54 15 34 10
Mean (Standard Deviation)
Unit of Measure: HAM-A Rating Score
4.17  (3.10) 6.29  (5.44) 11.35  (5.51) 5.80  (4.95) 8.42  (6.12) 6.19  (5.76)
2.Secondary Outcome
Title Clinical Global Impressions, Severity of Illness
Hide Description

The CGI provides an overall clinician-determined summary measure that takes into account a knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function.

The CGI is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.

Results of the "Placebo After Placebo" group in Phase 3 were not entered due to sample size limitations.

Time Frame Measured at Months 6 (Open Label), 12 (Double-Blind), 18 (Double-Blind, and 24 (Double-Blind Relapse)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analytic method was time to relapse analyses estimated using a discrete time Cox proportional hazards model.Chisquare analyses were used to contrast relapse or responder rates. In the case of small cell sizes, Fisher exact test replaced chisquare analysis.
Arm/Group Title Phase 1: Open-Label Venlafaxine XR Phase 2: Double-Blind Venlafaxine XR Phase 2: Double-Blind Placebo Phase 3: Double-Blind Drug After Drug Phase 3: Placebo After Drug Placebo After Placebo
Hide Arm/Group Description:
A 6-month administration of Venlafaxine XR that occurred between months 1 - 6 of study.
after receiving drug in phase 1, patients continued to receive drug in phase 2
After receiving drug in Phase 1, patients began receiving placebo in phase 2
after receiving drug in phases 1 and 2, patients continued to receive drug in phase 3
after receiving drug in phases 1 and 2, patients received placebo in phase 3
after receiving drug in phases 1 and placebo in phase 2, patients received placebo in phase 3
Overall Number of Participants Analyzed 268 82 54 15 34 10
Mean (Standard Deviation)
Unit of Measure: Severity Score
1.37  (0.65) 1.73  (1.27) 2.64  (1.25) 1.86  (1.01) 2.25  (1.17) 1.95  (1.31)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Venlafaxine XR
Hide Arm/Group Description Adverse events were expected with venlafaxine XR. AEs were reported at least once by at least 5% of the study population for all patients who entered treatment. None of the adverse events that were expected or that occurred were considered serious or life threatening.
All-Cause Mortality
Venlafaxine XR
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Venlafaxine XR
Affected / at Risk (%)
Total   0/268 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Venlafaxine XR
Affected / at Risk (%)
Total   219/268 (81.72%) 
Gastrointestinal disorders   
Constipation *  77/268 (28.73%) 
Diarrhea *  35/268 (13.06%) 
Flatulence *  66/268 (24.63%) 
Gas *  18/268 (6.72%) 
General disorders   
Abdominal Pain *  26/268 (9.70%) 
Decreased Orgasm *  55/268 (20.52%) 
Decreased Sex Drive *  68/268 (25.37%) 
Delayed Orgasm *  19/268 (7.09%) 
Drowsiness *  111/268 (41.42%) 
Dry mouth *  130/268 (48.51%) 
Faintness *  21/268 (7.84%) 
Fatigue *  76/268 (28.36%) 
Headache *  97/268 (36.19%) 
Increased sweating *  91/268 (33.96%) 
Insomnia *  82/268 (30.60%) 
Jitteriness *  74/268 (27.61%) 
Lightheadedness *  104/268 (38.81%) 
Muscle Aches *  50/268 (18.66%) 
Nausea *  89/268 (33.21%) 
Nightmares *  78/268 (29.10%) 
*
Indicates events were collected by non-systematic assessment
Increased attrition occurring as a function of trial length
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title: Karl Rickels, M.D.
Organization: UPENN
Phone: 215-746-6417
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Karl Rickels, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00183274     History of Changes
Other Study ID Numbers: MH65963
R01MH065963 ( U.S. NIH Grant/Contract )
First Submitted: September 12, 2005
First Posted: September 16, 2005
Results First Submitted: December 14, 2012
Results First Posted: November 30, 2016
Last Update Posted: January 16, 2017