Antidepressants Trial in Parkinson's Disease (ADepT-PD): Protocol for a Randomised Placebo-controlled Trial on the Effectiveness of Escitalopram and Nortriptyline on Depressive Symptoms in Parkinson's Disease

Overview

Journal BMC Neurol

Publisher Biomed Central

Specialty Neurology

Date 2022 Dec 12

PMID 36510237

Authors

A Schrag

C Carroll

G Duncan

S Molloy

L Grover

R Hunter

R Brown

N Freemantle

J Whipps

M A Serfaty

G Lewis

Affiliations

Soon will be listed here.

Abstract

Background: Depressive symptoms are common in patients with Parkinson's disease and depression is a significant predictor of functional impairment, reduced quality of life and general well-being in Parkinson's disease. Despite the high prevalence of depression, evidence on the effectiveness and tolerability of antidepressants in this population is limited. The primary aim of this trial is to establish the clinical and cost effectiveness of escitalopram and nortriptyline for the treatment of depression in Parkinson's disease.

Methods: This is a multi-centre, double-blind, randomised placebo-controlled trial in 408 people with Parkinson's disease with subsyndromal depression, major depressive disorder or persistent depressive disorder and a Beck Depression Inventory-II (BDI-II) score of 14 or above. Participants will be randomised into one of three groups, receiving either escitalopram, nortriptyline or placebo for 12 months. Trial participation is face-to-face, hybrid or remote. The primary outcome measure is the BDI-II score following 8 weeks of treatment. Secondary outcomes will be collected at baseline, 8, 26 and 52 weeks and following withdrawal, including severity of anxiety and depression scores as well as Parkinson's disease motor severity, and ratings of non-motor symptoms, cognitive function, health-related quality of life, levodopa-equivalence dose, changes in medication, overall clinical effectiveness, capability, health and social care resource use, carer health-related quality of life, adverse effects and number of dropouts.

Discussion: This trial aims to determine the effectiveness of escitalopram and nortriptyline for reducing depressive symptoms in Parkinson's disease over 8 weeks, to provide information on the effect of these medications on anxiety and other non-motor symptoms in PD and on impact on patients and caregivers, and to examine their effect on change in motor severity.

Trial Registration: ClinicalTrials.gov Identifier: NCT03652870 Date of registration - 29 August 2018.

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References

Weintraub D, Aarsland D, Chaudhuri K, Dobkin R, Leentjens A, Rodriguez-Violante M . The neuropsychiatry of Parkinson's disease: advances and challenges. Lancet Neurol. 2021; 21(1):89-102. PMC: 8800169. DOI: 10.1016/S1474-4422(21)00330-6. View

Heinonen E, Myllyla V . Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. Drug Saf. 1998; 19(1):11-22. DOI: 10.2165/00002018-199819010-00002. View

Skorvanek M, Martinez-Martin P, Kovacs N, Zezula I, Rodriguez-Violante M, Corvol J . Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients. Parkinsonism Relat Disord. 2018; 52:83-89. DOI: 10.1016/j.parkreldis.2018.03.027. View

Leo R . Movement disorders associated with the serotonin selective reuptake inhibitors. J Clin Psychiatry. 1996; 57(10):449-54. DOI: 10.4088/jcp.v57n1002. View

Peveler R, Kendrick T, Buxton M, Longworth L, Baldwin D, Moore M . A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. Health Technol Assess. 2005; 9(16):1-134, iii. DOI: 10.3310/hta9160. View

Jimenez-Jimenez F, Tejeiro J, Cabrera-Valdivia F, Alarcon J, Garcia-Albea E . Parkinsonism exacerbated by paroxetine. Neurology. 1994; 44(12):2406. DOI: 10.1212/wnl.44.12.2406. View

Devos D, Dujardin K, Poirot I, Moreau C, Cottencin O, Thomas P . Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. Mov Disord. 2008; 23(6):850-7. DOI: 10.1002/mds.21966. View

Tesei S, Antonini A, Canesi M, Zecchinelli A, Mariani C, Pezzoli G . Tolerability of paroxetine in Parkinson's disease: a prospective study. Mov Disord. 2000; 15(5):986-9. DOI: 10.1002/1531-8257(200009)15:5<986::aid-mds1034>3.0.co;2-i. View

Menza M, Dobkin R, Marin H, Mark M, Gara M, Buyske S . A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology. 2008; 72(10):886-92. PMC: 2677475. DOI: 10.1212/01.wnl.0000336340.89821.b3. View

10.

Christodoulou C, Papadopoulou A, Rizos E, Tournikioti K, Gonda X, Douzenis A . Extrapyramidal side effects and suicidal ideation under fluoxetine treatment: a case report. Ann Gen Psychiatry. 2010; 9:5. PMC: 2820028. DOI: 10.1186/1744-859X-9-5. View

11.

Richard I, McDermott M, Kurlan R, Lyness J, Como P, Pearson N . A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology. 2012; 78(16):1229-36. PMC: 3324323. DOI: 10.1212/WNL.0b013e3182516244. View

12.

Button K, Kounali D, Thomas L, Wiles N, Peters T, Welton N . Minimal clinically important difference on the Beck Depression Inventory--II according to the patient's perspective. Psychol Med. 2015; 45(15):3269-79. PMC: 4611356. DOI: 10.1017/S0033291715001270. View

13.

Reijnders J, Ehrt U, Weber W, Aarsland D, Leentjens A . A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord. 2007; 23(2):183-9. DOI: 10.1002/mds.21803. View

14.

Finkel S, Mintzer J, Dysken M, Krishnan K, Burt T, McRae T . A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil. Int J Geriatr Psychiatry. 2004; 19(1):9-18. DOI: 10.1002/gps.998. View

15.

Carriere I, Farre A, Norton J, Wyart M, Tzourio C, Noize P . Patterns of selective serotonin reuptake inhibitor use and risk of falls and fractures in community-dwelling elderly people: the Three-City cohort. Osteoporos Int. 2016; 27(11):3187-3195. DOI: 10.1007/s00198-016-3667-7. View

16.

Steur E . Increase of Parkinson disability after fluoxetine medication. Neurology. 1993; 43(1):211-3. DOI: 10.1212/wnl.43.1_part_1.211. View

17.

Collier T, Srivastava K, Justman C, Grammatopoulous T, Hutter-Paier B, Prokesch M . Nortriptyline inhibits aggregation and neurotoxicity of alpha-synuclein by enhancing reconfiguration of the monomeric form. Neurobiol Dis. 2017; 106:191-204. PMC: 5793922. DOI: 10.1016/j.nbd.2017.07.007. View

18.

Liu J, Dong J, Wang L, Su Y, Yan P, Sun S . Comparative efficacy and acceptability of antidepressants in Parkinson's disease: a network meta-analysis. PLoS One. 2013; 8(10):e76651. PMC: 3788746. DOI: 10.1371/journal.pone.0076651. View

19.

Anderson I . Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord. 2000; 58(1):19-36. DOI: 10.1016/s0165-0327(99)00092-0. View

20.

Vanderheyden J, Gonce M, Bourgeois P, Cras P, De Nayer A, Flamez A . Epidemiology of major depression in Belgian parkinsonian patients. Acta Neurol Belg. 2010; 110(2):148-56. View