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

Study Overview
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Brief Summary
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This study will assess the effectiveness of venlafaxine XR, randomized to either venlafaxine XR or placebo in preventing the relapse of generalized anxiety disorder after 6 months of treatment versus 12 months of treatment.

Detailed Description
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Generalized anxiety disorder (GAD) is a highly prevalent, chronic psychiatric disorder. Despite the fact that GAD frequently demands prolonged treatment with medication, very little is known about the benefits of long-term treatment. GAD is characterized by 6 months or more of exaggerated worry and tension that is unfounded or much more severe than the normal anxiety most people experience. People with GAD are unable to relax and often suffer from insomnia. Venlafaxine XR, a drug used to treat depression, has been shown to be effective in the short-term treatment of GAD. However, its benefits over a course of more than 8 weeks have not been assessed. This study will evaluate the effectiveness of venlafaxine XR in treating GAD on a long-term basis and preventing the relapse of GAD after 6 months of treatment versus 12 months of treatment. Participants in this double-blind study will first receive 6 months of open-label treatment with venlafaxine XR. Upon completion of this initial phase, participants will be randomly assigned to either continue on venlafaxine XR or begin taking placebo. After 12 months, participants taking venlafaxine XR will be randomly assigned to continue on the drug or switch to placebo. Participants will have 22 study visits over at least 18 months. Follow-up visits will occur 24 months after enrollment. Relapse of GAD will be assessed with the Hamilton Anxiety Scale and Global Severity and Improvement Scale. A variety of methods, including questionnaires and standardized scales, will be used to assess secondary outcomes.

Official Title
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Short-term Versus Long-term Treatment in Generalized Anxiety Disorder

Conditions
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Anxiety Disorders

Intervention / Treatment
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* Drug: Venlafaxine XR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GAD diagnosis by structured interview Hamilton Anxiety Scale score of 18 or MORE Clinical Global Impressions Severity Scale score of at least 4 Hamilton Depression Scale score of 18 or less Hamilton Depression Scale suicide item score less than 2 Use of an effective form of contraception throughout the study Exclusion Criteria: Hypersensitivity to venlafaxine XR History of seizures Episode of major depressive disorder in the previous 6 months History of any psychotic illness, bipolar disorder, or dementia Substance abuse and dependence during the past 6 months Other anxiety disorders with the exception of social phobia as long as GAD is primary Regular use of anxiolytics or antidepressants within 7 days of study onset Use of fluoxetine or monoamine oxidase inhibitors within 28 days of study onset (low dose usage of benzodiazepines will not prevent participation) Use of other psychotropic medication besides benzodiazepines during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Open-Label Group<br>6-month randomized phase of Venlafaxine XR at a flexible dose of 75 - 225 mg/d | Drug: Venlafaxine XR<br>* Six month intervention of Venlafaxine XR treatment with flexible range of 75 to 225 mg/d<br>* Other names: Lanvexin;|
| Active Comparator: Double-Blind Drug Group<br>6-month randomized, double-blind phase of Venlafaxine XR at a flexible dose of 75 - 225 mg/d occurring between months 6 - 12 of the study | Drug: Venlafaxine XR<br>* Six month intervention of Venlafaxine XR treatment with flexible range of 75 to 225 mg/d<br>* Other names: Lanvexin;|
| Placebo Comparator: Double-Blind Placebo Group<br>6-month randomized, double blind phase of placebo occurring between months 6 - 12 of the study | Drug: Placebo<br>* six month intervention with placebo drug<br>|
| Active Comparator: Double-Blind Drug-After-Drug Group<br>6-month randomized, double blind phase of Venlafaxine XR at a flexible dose of 75 - 225 mg/d occurring between months 13 - 19 of the study | Drug: Venlafaxine XR<br>* Six month intervention of Venlafaxine XR treatment with flexible range of 75 to 225 mg/d<br>* Other names: Lanvexin;|
| Placebo Comparator: Double-Blind Placebo-After-Drug Group<br>6-month randomized, double blind phase of placebo occurring between months 13 - 19 of the study | Drug: Placebo<br>* six month intervention with placebo drug<br>|
| Placebo Comparator: Double-Blind Placebo-After-Placebo Group<br>6-month randomized, double blind phase of placebo occurring between months 13 - 19 of the study | Drug: Placebo<br>* six month intervention with placebo drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Anxiety | 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. | Measured at Months 6 (Open Label), 12 (Double-Blind), and 18 (Double-Blind Relapse) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impressions, Severity of Illness | 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. | Measured at Months 6 (Open Label), 12 (Double-Blind), 18 (Double-Blind, and 24 (Double-Blind Relapse) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Generalized Anxiety Disorder, Chronic Mediation Treatment, Double-Blind, Placebo Controlled, Venlafaxine XR, Relapse