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

NCT ID: NCT00183274

Last Updated: 2017-01-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

268 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2009-09-30

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.

Conditions

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Anxiety Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Open-Label Group

6-month randomized phase of Venlafaxine XR at a flexible dose of 75 - 225 mg/d

Group Type ACTIVE_COMPARATOR

Venlafaxine XR

Intervention Type DRUG

Six month intervention of Venlafaxine XR treatment with flexible range of 75 to 225 mg/d

Double-Blind Drug Group

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

Group Type ACTIVE_COMPARATOR

Venlafaxine XR

Intervention Type DRUG

Six month intervention of Venlafaxine XR treatment with flexible range of 75 to 225 mg/d

Double-Blind Placebo Group

6-month randomized, double blind phase of placebo occurring between months 6 - 12 of the study

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

six month intervention with placebo drug

Double-Blind Drug-After-Drug Group

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

Group Type ACTIVE_COMPARATOR

Venlafaxine XR

Intervention Type DRUG

Six month intervention of Venlafaxine XR treatment with flexible range of 75 to 225 mg/d

Double-Blind Placebo-After-Drug Group

6-month randomized, double blind phase of placebo occurring between months 13 - 19 of the study

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

six month intervention with placebo drug

Double-Blind Placebo-After-Placebo Group

6-month randomized, double blind phase of placebo occurring between months 13 - 19 of the study

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

six month intervention with placebo drug

Interventions

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Venlafaxine XR

Six month intervention of Venlafaxine XR treatment with flexible range of 75 to 225 mg/d

Intervention Type DRUG

Placebo

six month intervention with placebo drug

Intervention Type DRUG

Other Intervention Names

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selective serotonin and norepinephrine reuptake inhibitors Effexor Effexor XR Venlafaxine hydrochloride extended release Trevilor Lanvexin

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Karl Rickels

Professor of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Karl Rickels, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

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University of Pennsylvania, 3535 Market Street, Suite 670

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Rickels K, Etemad B, Rynn MA, Lohoff FW, Mandos LA, Gallop R. Remission of generalized anxiety disorder after 6 months of open-label treatment with venlafaxine XR. Psychother Psychosom. 2013;82(6):363-71. doi: 10.1159/000351410. Epub 2013 Sep 20.

Reference Type BACKGROUND
PMID: 24061331 (View on PubMed)

Rickels K, Etemad B, Khalid-Khan S, Lohoff FW, Rynn MA, Gallop RJ. Time to relapse after 6 and 12 months' treatment of generalized anxiety disorder with venlafaxine extended release. Arch Gen Psychiatry. 2010 Dec;67(12):1274-81. doi: 10.1001/archgenpsychiatry.2010.170.

Reference Type RESULT
PMID: 21135327 (View on PubMed)

Jung J, Tawa EA, Muench C, Rosen AD, Rickels K, Lohoff FW. Genome-wide association study of treatment response to venlafaxine XR in generalized anxiety disorder. Psychiatry Res. 2017 Aug;254:8-11. doi: 10.1016/j.psychres.2017.04.025. Epub 2017 Apr 14.

Reference Type DERIVED
PMID: 28437668 (View on PubMed)

Saung WT, Narasimhan S, Lohoff FW. Lack of influence of DAT1 and DRD2 gene variants on antidepressant response in generalized anxiety disorder. Hum Psychopharmacol. 2014 Jul;29(4):316-21. doi: 10.1002/hup.2404. Epub 2014 Apr 10.

Reference Type DERIVED
PMID: 24723432 (View on PubMed)

Cooper AJ, Narasimhan S, Rickels K, Lohoff FW. Genetic polymorphisms in the PACAP and PAC1 receptor genes and treatment response to venlafaxine XR in generalized anxiety disorder. Psychiatry Res. 2013 Dec 30;210(3):1299-300. doi: 10.1016/j.psychres.2013.07.038. Epub 2013 Aug 22.

Reference Type DERIVED
PMID: 23972788 (View on PubMed)

Cooper AJ, Rickels K, Lohoff FW. Association analysis between the A118G polymorphism in the OPRM1 gene and treatment response to venlafaxine XR in generalized anxiety disorder. Hum Psychopharmacol. 2013 May;28(3):258-62. doi: 10.1002/hup.2317. Epub 2013 May 8.

Reference Type DERIVED
PMID: 23658070 (View on PubMed)

Lohoff FW, Narasimhan S, Rickels K. Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics J. 2013 Oct;13(5):464-9. doi: 10.1038/tpj.2012.33. Epub 2012 Aug 21.

Reference Type DERIVED
PMID: 22907732 (View on PubMed)

Narasimhan S, Aquino TD, Multani PK, Rickels K, Lohoff FW. Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder. Psychiatry Res. 2012 Jun 30;198(1):112-5. doi: 10.1016/j.psychres.2011.12.034. Epub 2012 Mar 13.

Reference Type DERIVED
PMID: 22417933 (View on PubMed)

Lohoff FW, Aquino TD, Narasimhan S, Multani PK, Etemad B, Rickels K. Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics J. 2013 Feb;13(1):21-6. doi: 10.1038/tpj.2011.47. Epub 2011 Oct 18.

Reference Type DERIVED
PMID: 22006095 (View on PubMed)

Narasimhan S, Aquino TD, Hodge R, Rickels K, Lohoff FW. Association analysis between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and treatment response to venlafaxine XR in generalized anxiety disorder. Neurosci Lett. 2011 Oct 10;503(3):200-2. doi: 10.1016/j.neulet.2011.08.035. Epub 2011 Aug 26.

Reference Type DERIVED
PMID: 21889574 (View on PubMed)

Other Identifiers

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R01MH065963

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MH65963

Identifier Type: -

Identifier Source: org_study_id

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