A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease

I. H. Richard, M. P. McDermott, R. Kurlan, J. M. Lyness, P. G. Como, N. Pearson, S. A. Factor, J. Juncos, C. Serrano Ramos, M. Brodsky, C. Manning, L. Marsh, L. Shulman, H. H. Fernandez, K. J. Black, M. Panisset, C. W. Christine, W. Jiang, C. Singer, S. HornR. Pfeiffer, D. Rottenberg, J. Slevin, L. Elmer, D. Press, H. C. Hyson, W. McDonald

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

Objective: To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD). Methods: A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39). Subjects met DSM-IV criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored 12 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Subjects were followed for 12 weeks (6-week dosage adjustment, 6-week maintenance). Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR. The primary outcome measure was change in the HAM-D score from baseline to week 12. Results: Treatment effects (relative to placebo), expressed as mean 12-week reductions in HAM-D score, were 6.2 points (97.5% confidence interval [CI] 2.2 to 10.3, p = 0.0007) in the paroxetine group and 4.2 points (97.5% CI 0.1 to 8.4, p = 0.02) in the venlafaxine XR group. No treatment effects were seen on motor function. Conclusions: Both paroxetine and venlafaxine XR significantly improved depression in subjects with PD. Both medications were generally safe and well tolerated and did not worsen motor function. Classification of Evidence: This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD.

Original languageEnglish (US)
Pages (from-to)1229-1236
Number of pages8
JournalNeurology
Volume78
Issue number16
DOIs
StatePublished - Apr 17 2012

Bibliographical note

Funding Information:
Study funding: Supported by NIH/NINDS R01 NS046487 and the General Clinical Research Center at Johns Hopkins University School of Medicine (National Center for Research Resources/NIH M01-RR00052). Wyeth Pharmaceuticals provided venlafaxine XR and matching placebo. Glaxo-Smith Kline provided paroxetine.

Funding Information:
Dr. Richard serves on a scientific advisory board for the Michael J. Fox Foundation; has received a speaker honorarium from Teva Pharmaceutical Industries Ltd.; and receives/has received research support from Neurologix, Inc., Eli Lilly and Company, the NIH/NINDS, Cornell University, and the Michael J. Fox Foundation. Dr. McDermott serves on data safety monitoring boards for Isis Pharmaceuticals, Inc., Biogen Idec, the ALS Association/FDA, and the Muscular Dystrophy Association; serves on the editorial board of Movement Disorders; has served as a consultant for the New York State Department of Health, Teva Pharmaceutical Industries, Ltd., Synosia, Inc., Smith and Nephew, Inc., and IMPAX Laboratories, Inc.; and receives/has received research support from Forest Laboratories, Inc., Medivation, Inc., NeuroSearch, Boehringer Ingelheim, Pfizer Inc, Endo Pharmaceuticals, the NIH, the CDC, the FDA, the Michael J. Fox Foundation, Spinal Muscular Atrophy Foundation, Muscular Dystrophy Association, and American Dental Association. Dr. Kurlan serves as Supplement Editor for Neurology® and receives research support from Boehringer Ingelheim, Kyowa Hakko Kirin Pharma, Inc., Neurologix, Inc., and the NIH. Dr. Lyness serves on data safety monitoring board for the NIH/NIA; serves as Consulting Editor for Psychology and Aging; and receives/has received research support from the NIH (NIMH, NIA, NINDS). Dr. Como and N. Pearson report no disclosures. Dr. Factor serves as a Section Editor for Current Treatment Options in Neurology and Clinical Neurology and Neuroscience; receives publishing royalties for Parkinson's Disease Diagnosis and Clinical Management (Demos, 2008) and Drug Induced Movement Disorders (Blackwell Futura, 2005); receives research support from Teva Pharmaceutical Industries Ltd., Ipsen, Merck Serono, Ceregene, the NIH (NHLBI, NINDS), and the Michael J. Fox Foundation; and has served as an expert witness in a medico-legal proceeding. Dr. Juncos has served on the speakers' bureaus of UCB and Novartis and receives research support from the NIH (NINDS, NICHD). Dr. Serrano Ramos has received research support from the NIH. Dr. Brodsky has served on scientific advisory boards for Ipsen, Merz Pharmaceuticals, LLC, and Teva Pharmaceutical Industries Ltd.; has received speaker honoraria from Teva Pharmaceutical Industries Ltd. and Medtronic, Inc.; and serves on speakers' bureaus for Teva Pharmaceutical Industries Ltd., Allergan, Inc., Merz Pharmaceuticals, LLC, and Ipsen. Dr. Manning reports no disclosures. Dr. Marsh serves on scientific advisory boards for Merck Serono, Ovation Pharmaceuticals (Lundbeck Inc.), ACADIA Pharmaceuticals, Boehringer Ingelheim, National Parkinson Foundation, American Parkinson's Disease Association, and Parkinson Study Group; serves on the editorial board of the Journal of Parkinson's Disease; receives publishing royalties for Psychiatric Issues in Parkinson's Disease: A Practical Guide (Taylor & Francis/Informa, 2005); serves as a consultant for Merck Serono, Ovation Pharmaceutical (Lundbeck Inc.), ACADIA Pharmaceuticals, and Boehringer Ingelheim; and receives/has received research support from Forest Laboratories, Inc., Eli Lilly and Company, Boehringer Ingelheim, the NIH, the American Psychiatric Association, Baylor College of Medicine, and the Michael J. Fox Foundation. Dr. Shulman serves as Editor-in-Chief of the Neurology Now Patient Book Series and on the editorial advisory board of Neurology Now; receives publishing royalties for Parkinson's Disease: A Complete Guide for Patients and Families (Johns Hopkins University Press, 2000, 2007); receives research support from Teva Pharmaceutical Industries Ltd., the NIH, and the Michael J. Fox Foundation; and has served as a consultant in medico-legal proceedings. Dr. Fernandez serves on scientific advisory boards for Solvay Pharmaceuticals, Inc. and EMD Serono, Inc.; has received funding for travel or speaker honoraria from Medical Communications Media, Health Professions Conferencing, Ipsen, Merz Pharmaceuticals, LLC, and US World Meds; serves as Medical Editor of the Movement Disorders Society's Web site; is patent co-owner of COMPRESS, a neurosurgical candidate selection tool; receives publishing royalties from Demos, Manson, and Springer; and receives/has received research support from Abbott, ACADIA Pharmaceuticals, Biotie Therapeutics, EMD Serono, Inc., Novartis, Teva Pharmaceutical Industries Ltd., the NIH/NINDS, Huntington Study Group, Movement Disorders Society, Parkinson Study Group, the Michael J. Fox Foundation, National Parkinson Foundation, and Society of Progressive Supranuclear Palsy. Dr. Black serves on a scientific advisory board for the Tourette Syndrome Association; serves on the editorial advisory board of The Open Neuroimaging Journal; is listed as author on patents re: Novel methods for medicinal dosage determination and diagnosis and A2A antagonists as cognition and motor function enhancers; has served as a consultant for Synosia Therapeutics, Merck Serono, and Gerson Lehman Group; and receives/has received research support from Synosia Therapeutics, ACADIA Pharmaceuticals, the NIH (NIDDK, NIMH, NCRR), the Tourette Syndrome Association, and the McDonnell Center for Systems Neuroscience at Washington University. Dr. Panisset serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Novartis, Allergan, Inc., and Merz Pharmaceuticals, LLC; has received funding for travel or speaker honoraria from Merz Pharmaceuticals, LLC, Medtronic, Inc., and Teva Pharmaceutical Industries Ltd.; and receives research support from Allon Therapeutics, Inc. and Teva Pharmaceutical Industries Ltd. Dr. Christine receives research/salary support from Genzyme Corporation, Kyowa Hakko Kirin Pharma, Inc., Eisai Inc., and the NIH/NINDS. Dr. Jiang reports no disclosures. Dr. Singer serves on scientific advisory boards for Lundbeck Inc., Merz Pharmaceuticals, LLC, and Ipsen; has received funding for travel from Ipsen; and receives/has received research support from Schwartz Biomedical, LLC, Merz Pharmaceuticals, LLC, Teva Pharmaceutical Industries Ltd., the NIH, Parkinson Study Group, Huntington Study Group, and National Parkinson Foundation. Dr. Horn reports no disclosures. Dr. Pfeiffer serves on the scientific advisory board for the National Parkinson Foundation; serves as Co-Editor in Chief of Parkinsonism and Related Disorders and on the editorial board of the Journal of Parkinson's Disease; receives publishing royalties for Parkinson's Disease (Taylor & Francis, 2008-present), Parkinson's Disease and Nonmotor Dysfunction (Humana, 2008–present), and Neuro-Gastroenterology (Butterworth-Heinemann, 2008); serves as a consultant for Solvay Pharmaceuticals, Inc., Theravance Inc., Genactis, Schlesinger Associates, and UCB; serves on speakers' bureaus for Boehringer Ingelheim, Novartis, and Teva Pharmaceutical Industries Ltd.; receives research support from Novartis, Boehringer Ingelheim, UCB/SCHWARZ PHARMA, Santhera Pharmaceuticals, Molecular Biometrics, Columbia University, Weill Cornell Medical College, Northwestern University, Indiana University, Parkinson Study Group, and the Michael J. Fox Foundation; and has served as a consultant in medico-legal proceedings. Dr. Rottenberg reports no disclosures. Dr. Slevin serves/has served on speakers' bureau for Boehringer Ingelheim, Novartis, and Teva Pharmaceutical Industries Ltd.; and receives/has received research support from Solvay Pharmaceuticals, Inc. and the NIH. Dr. Elmer has received research support from Teva Pharmaceutical Industries Ltd. and serves on speakers' bureaus for Teva Pharmaceutical Industries Ltd., GlaxoSmithKline, Novartis, and UCB. Dr. Press receives/has received research support from the NIH (NIMH, NIA), the Milton Fund, and the Harvard Center for Neurodegeneration and Repair. Dr. Hyson has served on scientific advisory boards for Biogen Idec; and has received speaker honoraria from Merz Pharmaceuticals, LLC and Biogen Idec. Dr. McDonald serves as Triage Editor for American Journal of Geriatric Psychiatry and on the editorial board of the Journal of ECT; serves as a consultant for Cervel Neurotech; and receives/has received research support from the NIH/NIMH, GlaxoSmithKline, Wyeth, Boehringer Ingelheim, and Janssen.

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