Study of Antidepressants in Parkinson's Disease - Full Text View

Purpose

The purpose of this study is to find out if two antidepressant medications, paroxetine and venlafaxine, can help control depression in Parkinson's disease, and if these medications affect the motor symptoms of Parkinson's disease such as tremor, stiffness, slowness, and balance.

Condition	Intervention	Phase
Parkinson Disease Depression	Drug: paroxetine Drug: venlafaxine Other: placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Study of Antidepressants in Parkinson's Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Parkinson disease Perry syndrome

MedlinePlus related topics: Antidepressants Depression Parkinson's Disease Tremor

Drug Information available for: Paroxetine Paroxetine hydrochloride Venlafaxine Venlafaxine hydrochloride Paroxetine hydrochloride hemihydrate Paroxetine Mesylate

U.S. FDA Resources

Further study details as provided by University of Rochester:

Primary Outcome Measures:

Change in Hamilton Depression Rating Scale (HAM-D) Scores [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Change in Hamilton Rating Scale for Depression over 12 weeks. Hamilton Depression Rating Scale ranges from 0-50. Higher scores represent more significant depression. Mild depression ranges from 8-13, moderate depression from 14-18, severe 19-22 and very severe any score over 23.

Secondary Outcome Measures:

Change in Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Montgomery-Asberg Depression Rating Scale ranges from 0-60. Higher score indicates more severe depression. 0-6 normal, 7-19 mild depression, 20-34 moderate depression, greater than 34 severe depression.
Change in Beck Depression Inventory II (BDI-II) [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Beck Depression Inventory II ranges from 0-63. Higher score indicates more severe depression. 0-13 minimal depression, 14-19 mild depression, 20-28 moderate depression, 29-63 severe depression.
Change in Geriatric Depression Rating Scale (GDS) [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Geriatric Depression Scale ranges from 0-30. Higher score indicates more severe depression. 0-9 normal, 10-19 mild depression, 20-30 severe depression.
Change in Brief Psychiatric Rating Scale (BPRS) [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: Yes ]
Brief Psychiatric Rating Scale. Maximum score 126. Higher score indicates greater psychiatric difficulties.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Unified Parkinson's Disease Rating Scale. Higher score indicates more severe Parkinson's disease symptoms. Total maximum = 176. Mental maximum = 52, Activities of Daily Living maximum = 52, Motor maximum = 72. Minimum = 0.
Change in Snaith Clinical Anxiety Scale (CAS) [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Snaith Clinical Anxiety Scale. Range 0-21. Higher scores indicate increased anxiety. Score greater than 8 indicates clinical anxiety.
Change in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Pittsburgh Sleep Quality Index scores range from 0-21, with higher scores indicating severe sleep difficulties.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) - Motor [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Unified Parkinson's Disease Rating Scale - Motor has a maximum score of 72, minimum score of 0. Higher score indicates more severe Parkinson's disease symptoms.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) - Tremor [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Unified Parkinson's Disease Rating Scale - Tremor subscale ranges from 0-23. Higher score indicates more severe Parkinson's disease symptoms.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) - Bulbar [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Unified Parkinson's Disease Rating Scale - Bulbar maximum score 24, minimum score of 0. Higher score indicates more severe Parkinson's disease symptoms.
Change in Parkinson's Disease Questionnaire (PDQ) - 39 - Overall [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Parkinson's Disease Questionnaire (PDQ-39) Total. Range 0-100. Lower score indicates a better perceived health status.
Change in Parkinson's Disease Questionnaire (PDQ) - 39 - Emotional Well-Being [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Parkinson's Disease Questionnaire (PDQ-39) - Emotional Well-Being maximum score 24, minimum score of 0.Lower score indicates a better perceived health status.
Change in Short Form 36 Health Survey - Mental Component Summary [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Short Form 36 Health Survey. Range 0-100. Higher score indicates a better perceived quality of life.
Change in Short Form 36 Health Survey - Vitality [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Short Form 36 Health Survey - Vitality subscale ranges from 0-100. Higher score indicates a better perceived quality of life.
Change in Short Form 36 Health Survey - Role-Emotional [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Short Form 36 Health Survey - Emotional subscale ranges from 0-100. Higher score indicates a better perceived quality of life.
Change in Short Form 36 Health Survey - Mental Health [ Time Frame: from the beginning (0 weeks) to end (12 weeks) of the double-blind phase ] [ Designated as safety issue: No ]
Short Form 36 Health Survey - Mental Health subscale ranges from 0-100. Higher score indicates a better perceived quality of life.

Enrollment:	115
Study Start Date:	June 2005
Study Completion Date:	November 2009
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: paroxetine Paroxetine and venlafaxine will be compared to placebo over 12 weeks.	Drug: paroxetine Paroxetine 10 mg tablets or matching placebo given once a day for the first two weeks. If depression is not being effectively treated then the paroxetine or matching placebo will be increased to 20 mg, followed by a 10 mg increase every two weeks (if tolerated). Dosage for this study will not exceed 40 mg. Other Name: Paxil
Active Comparator: venlafaxine extended release Paroxetine and venlafaxine will be compared to placebo over 12 weeks.	Drug: venlafaxine Venlafaxine XR 37.5 mg capsules or matching placebo given once a day for the first two weeks. If depression is not being effectively treated then the venlafaxine XR capsules or matching placebo will be increased to 75 mg followed by 75 mg increments every 2 weeks (if tolerated). Dosage for this study will not exceed 225 mg. Other Name: Effexor XR
Placebo Comparator: placebo Paroxetine and venlafaxine will be compared to placebo over 12 weeks.	Other: placebo an inactive substance

Detailed Description:

Nearly 50 percent of individuals with Parkinson's disease (PD) suffer from depression—a condition that causes disability and can reduce quality of life. The University of Rochester Medical Center is conducting a research study of antidepressant medications to find out more about how to treat depression in PD. Antidepressant medications have not been adequately studied in persons with PD.

The purpose of this study is to find out if the antidepressant medications paroxetine and venlafaxine can help control depression in PD and whether or not these medications affect the motor symptoms of PD such as tremor, stiffness, slowness, and balance.

This is a randomized, double blind, placebo-controlled, 12-week study of paroxetine immediate release (Paxil) and venlafaxine extended release (Effexor XR). Paroxetine and venlafaxine XR are drugs that have been approved by the Food and Drug Administration (FDA) and are available by prescription. Paroxetine and venlafaxine XR have been shown to be effective in treating depression in the general population. Two hundred, twenty-eight persons will be enrolled among 15 medical centers throughout the United States and Canada. Each person will participate in the trial for 12 weeks. Each participant will be randomly assigned to take either paroxetine or venlafaxine, or a placebo.

Eligibility

Ages Eligible for Study:	30 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

To be eligible you must be:

30 years old or older
diagnosed with Parkinson's disease
experiencing symptoms of depression such as sadness, decreased energy, or problems sleeping

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086190

Locations

United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21250
Johns Hopkins University
Baltimore, Maryland, United States, 21218
United States, Massachusetts
Beth Israel Deaconess Medical Center, Dept. of Neurology E/KS 430, 330 Brookline Avenue
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
University of Rochester
Rochester, New York, United States, 14627
United States, Ohio
Medical University of Ohio
Toledo, Ohio, United States
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Tennessee
University of Tennessee-Memphis
Memphis, Tennessee, United States, 38163
United States, Texas
Baylor College of Medicine, 6550 Fannin, Suite 1801
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22901
Canada, Ontario
London Health Sciences Centre, University Campus Room A10-325, 339 Windermere Road
London, Ontario, Canada, N6A 5A5
Canada, Quebec
Hotel-Dieu Hospital-CHUM
Montreal, Quebec, Canada, H2W 1T8
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936

Sponsors and Collaborators

University of Rochester

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	Irene Richard, MD	University of Rochester
Principal Investigator:	William McDonald, MD	Co-Principal Investigator--Emory University School of Medicine

More Information

Publications:

Dooneief G, Mirabello E, Bell K, Marder K, Stern Y, Mayeux R. An estimate of the incidence of depression in idiopathic Parkinson's disease. Arch Neurol. 1992 Mar;49(3):305-7.

Liu CY, Wang SJ, Fuh JL, Lin CH, Yang YY, Liu HC. The correlation of depression with functional activity in Parkinson's disease. J Neurol. 1997 Aug;244(8):493-8.

Kuopio AM, Marttila RJ, Helenius H, Toivonen M, Rinne UK. The quality of life in Parkinson's disease. Mov Disord. 2000 Mar;15(2):216-23.

Phillips P. Keeping depression at bay helps patients with Parkinson disease. JAMA. 1999 Sep 22-29;282(12):1118-9.

Global Parkinson's Disease Survey Steering Committee. Factors impacting on quality of life in Parkinson's disease: results from an international survey. Mov Disord. 2002 Jan;17(1):60-7.

Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, Bienfait K, Dicke A. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology. 2009 Mar 10;72(10):886-92. doi: 10.1212/01.wnl.0000336340.89821.b3. Epub 2008 Dec 17.

Yeragani VK, Roose S, Mallavarapu M, Radhakrishna RK, Pesce V. Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on measures of nonlinearity and chaos of heart rate. Neuropsychobiology. 2002;46(3):125-35.

Yeragani VK, Pesce V, Jayaraman A, Roose S. Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on long-term heart rate variability measures. Biol Psychiatry. 2002 Sep 1;52(5):418-29.

Nelson JC, Kennedy JS, Pollock BG, Laghrissi-Thode F, Narayan M, Nobler MS, Robin DW, Gergel I, McCafferty J, Roose S. Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease. Am J Psychiatry. 1999 Jul;156(7):1024-8.

Simons JA. Fluoxetine in Parkinson's disease. Mov Disord. 1996 Sep;11(5):581-2.

Steur EN. Increase of Parkinson disability after fluoxetine medication. Neurology. 1993 Jan;43(1):211-3.

Jiménez-Jiménez FJ, Tejeiro J, Martínez-Junquera G, Cabrera-Valdivia F, Alarcón J, García-Albea E. Parkinsonism exacerbated by paroxetine. Neurology. 1994 Dec;44(12):2406.

Salzman C. Pharmacologic treatment of depression in the elderly. J Clin Psychiatry. 1993 Feb;54 Suppl:23-8. Review.

Altamura AC, De Novellis F, Guercetti G, Invernizzi G, Percudani M, Montgomery SA. Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial. Int J Clin Pharmacol Res. 1989;9(6):391-6.

Cohn CK, Shrivastava R, Mendels J, Cohn JB, Fabre LF, Claghorn JL, Dessain EC, Itil TM, Lautin A. Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. J Clin Psychiatry. 1990 Dec;51 Suppl B:28-33.

Dunner DL, Cohn JB, Walshe T 3rd, Cohn CK, Feighner JP, Fieve RR, Halikas JP, Hartford JT, Hearst ED, Settle EC Jr, et al. Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression. J Clin Psychiatry. 1992 Feb;53 Suppl:57-60.

Guillibert E, Pelicier Y, Archambault JC, Chabannes JP, Clerc G, Desvilles M, Guibert M, Pagot R, Poisat JL, Thobie Y. A double-blind, multicentre study of paroxetine versus clomipramine in depressed elderly patients. Acta Psychiatr Scand Suppl. 1989;350:132-4.

Hirschfeld RM. Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs. J Clin Psychiatry. 1999 May;60(5):326-35. Review.

Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001 Nov;62(11):869-77.

Gentil V, Kerr-Correa F, Moreno R, D'Arrigo Busnello E, De Campos JA, Juruena MF, Lafer B, Moreno DH, De Cassia Rodrigues RL, Tiosso A, Benedictis E. Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. J Psychopharmacol. 2000 Mar;14(1):61-6.

Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. No abstract available.

HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62. No abstract available.

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9.

Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996 Dec;67(3):588-97.

Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-83;17(1):37-49.

Uc EY, McDermott MP, Marder KS, Anderson SW, Litvan I, Como PG, Auinger P, Chou KL, Growdon JC; Parkinson Study Group DATATOP Investigators. Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort. Neurology. 2009 Nov 3;73(18):1469-77. doi: 10.1212/WNL.0b013e3181bf992f.

Lachin JM. Introduction to sample size determination and power analysis for clinical trials. Control Clin Trials. 1981 Jun;2(2):93-113.

McDonald WM, Holtzheimer PE, Haber M, Vitek JL, McWhorter K, Delong M. Validity of the 30-item geriatric depression scale in patients with Parkinson's disease. Mov Disord. 2006 Oct;21(10):1618-22.

Okun MS, Fernandez HH. Will tricyclic antidepressants make a comeback for depressed Parkinson disease patients? Neurology. 2009 Mar 10;72(10):868-9. doi: 10.1212/01.wnl.0000338145.24512.02. Epub 2008 Dec 17.

Brunoni AR, Lopes M, Kaptchuk TJ, Fregni F. Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis. PLoS One. 2009;4(3):e4824. doi: 10.1371/journal.pone.0004824. Epub 2009 Mar 18. Review.

Senn S, Julious S. Measurement in clinical trials: a neglected issue for statisticians? Stat Med. 2009 Nov 20;28(26):3189-209. doi: 10.1002/sim.3603.

Responsible Party:	Irene Richard, Irene Richard, MD, University of Rochester
ClinicalTrials.gov Identifier:	NCT00086190 History of Changes
Other Study ID Numbers:	R01NS046487
Study First Received:	June 28, 2004
Results First Received:	January 11, 2012
Last Updated:	January 3, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Rochester:

Parkinson disease
depression
Parkinson's disease

paroxetine
venlafaxine
antidepressant

Additional relevant MeSH terms:

Depression
Depressive Disorder
Parkinson Disease
Behavioral Symptoms
Mood Disorders
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Antidepressive Agents

Paroxetine
Venlafaxine
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation

ClinicalTrials.gov processed this record on June 18, 2013

Study of Antidepressants in Parkinson's Disease (SAD-PD)