Antidepressants Trial in Parkinson's Disease

NCT03652870 | Completed Phase 3 DMC

• 1 other identifier: 18/0279
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomised trial in a NHS setting, comparing the clinical effectiveness and cost-effectiveness of the selective serotonin reuptake inhibitor, escitalopram, and of the tricyclic antidepressant, nortriptyline, to placebo, undertaken in a real-life setting in addition to standard psychological care for the treatment of patients with depression in Parkinson's disease. Participants will be randomly allocated 1:1:1 to receive escitalopram or nortriptyline or placebo.

Conditions

Depression; Parkinson Disease

Keywords

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Depressive symptoms

  Measured using the Beck Depression Inventory II to assess the severity of depression

  8 weeks

Secondary Outcomes (16)

• Level of depression

  26 and 52 Weeks

• Severity of depression

  8, 26 and 52 Weeks

• Number of patients suffering side effects

  8, 26 and 52 Weeks

• Number of participants suffering side effects

  8, 26 and 52 Weeks

• Overall clinical effectiveness

  8, 26 and 52 Weeks

Study Arms (3)

Nortriptyline

ACTIVE COMPARATOR

25mg tablet to be escalated from one tablet per day to a maximum of 4 tablets per day

Drug: Nortriptyline

Escitalopram

ACTIVE COMPARATOR

5mg tablet to be escalated from one tablet per day to a maximum of 4 tablets per day

Drug: Escitalopram

Placebo

PLACEBO COMPARATOR

The placebo tablet consists of lactose and magnesium stearate. One tablet to be escalated from one tablet per day to a maximum of 4 tablets per day

Drug: Placebo

Interventions

Nortriptyline DRUG

A medication used to treat conditions such as depression

Also known as: Nortriptyline 25mg

Nortriptyline

Escitalopram DRUG

A medication used to treat conditions such as depression

Also known as: Escitalopram 5mg

Escitalopram

Placebo DRUG

Lactose and magnesium stearate tablet to be used as a placebo.

Also known as: Placebo oral tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of idiopathic Parkinson's Disease, based on a history and neurological exam performed by the enrolling investigator with presence of at least two of the three cardinal signs of Parkinson's Disease: rigidity, bradykinesia, and rest tremor with no evidence of diagnostic alternatives. Patients who have been treated with levodopa must have demonstrated a clear response.
• Aged 18 years old or above
• Fulfilling diagnostic (DSM-V) criteria for a depressive disorder (i.e., major depressive disorder or persistent depressive disorder) or operationally defined subsyndromal depression (presence of two or more depressive symptoms at threshold or subthreshold levels, at least one of which has to include depressed mood or anhedonia
• Beck Depression Inventory-II (BDI-II) score ≥14
• Written informed consent provided
• Treatment with antiparkinsonian medication is optimised or stable for at least 4 weeks before date of randomisation and there are no plans to change up to primary endpoint (8 weeks).

You may not qualify if:

• Women who are pregnant, breastfeeding or of childbearing potential without effective contraception (hormonal or barrier method of birth control; or abstinence)
• Patients not able to communicate answers to the self-rating questionnaires
• Patients with Montreal Cognitive Assessment (MoCA) score \<16 or without capacity to consent
• Treatment with an antidepressant within 4 weeks of enrolment (except for a small dose of amitriptyline up to 50 mg for indications other than depression)
• Patients with known severe liver failure.
• Absolute contraindications to escitalopram or nortriptyline. These include:
• Patients with known QT-interval prolongation or congenital long QT syndrome.
• Recent myocardial infarction (\<3 months), any degree of heart block or other cardiac arrhythmias precluding treatment with nortriptyline or escitalopram according to clinical judgement.
• Medications contraindicated on nortriptyline or escitalopram. These include:
• Non-selective and selective irreversible monoamine oxidase inhibitors (MAOIs) within 14 days. However, the antiparkinsonian selective reversible MAO-B inhibitors rasagiline, selegiline and safinamide are not contraindicated.
• Concomitant QT prolonging drugs, including domperidone, apomorphine at high doses (single dose or hourly rate of \>6mg), certain neuroleptics (not quetiapine or clozapine), quinine, class IA and III antiarrhythmics (amiodarone, dronedarone and disopyramide), the antihistamines astemizole, mizolastine, the antimicrobial agents sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, anti-malarian treatment),and some antiretrovirals.
• Patients indicating active suicidal ideation or intent on the BDI-II item 9 and who, after clinical review of risk using the standardised Suicide Risk Management Protocol, need to be referred for immediate treatment.
• Participation in another clinical trial of an investigational medicinal product or device within the last 30 days.
• Any clinical condition which in the opinion/ clinical judgement of the investigator would make the patient unsuitable for the trial due to safety concerns.

Sponsors & Collaborators

• University College, London: lead
• London North West Healthcare NHS Trust: collaborator
• King's College London: collaborator
• University Hospital Plymouth NHS Trust: collaborator
• NHS Lothian: collaborator

Study Sites (1)

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Related Publications (2)

• Schrag A, Carroll C, Lewis G, Serfaty M, Duncan G, Molloy S, Whipps J, McLennan B, Weng JYJ, Hunter RM, Clarke CS, Freemantle N, Embleton-Thirsk A. Effectiveness of Escitalopram and Nortriptyline on Depressive Symptoms in Parkinson's disease: the ADepT-PD RCT pilot. Health Technol Assess. 2025 Nov;29(57):1-78. doi: 10.3310/HFDO7575.

  PMID: 41217862 DERIVED

• Schrag A, Carroll C, Duncan G, Molloy S, Grover L, Hunter R, Brown R, Freemantle N, Whipps J, Serfaty MA, Lewis G. 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. BMC Neurol. 2022 Dec 12;22(1):474. doi: 10.1186/s12883-022-02988-5.

  PMID: 36510237 DERIVED

MeSH Terms

Conditions

Depression; Parkinson Disease

Interventions

Nortriptyline; Escitalopram

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Anette Schrag

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 29, 2018
• Study Start: March 5, 2021
• Primary Completion: January 23, 2023
• Study Completion: April 30, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)