Antidepressants Trial in Parkinson's Disease

• Status: Recruiting
• Trial end date: 2023-04-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Collaborators: King's College London; London North West Healthcare NHS Trust; NHS Lothian; University Hospital Plymouth NHS Trust
• Treatments: Citalopram; Dexetimide; Nortriptyline

Criteria

Inclusion Criteria:

1. 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.

2. Aged 18 to 85 years

3. 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

4. Beck Depression Inventory-II (BDI-II) score ≥14

5. Written informed consent provided

Exclusion Criteria:

1. Women who are pregnant, breastfeeding or of childbearing potential without effective contraception (hormonal or barrier method of birth control; or abstinence)

2. Patients not able to communicate answers to the self-rating questionnaires

3. Patients with Montreal Cognitive Assessment (MoCA) score <16 or without capacity to consent

4. 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)

5. Absolute contraindications to escitalopram or nortriptyline

6. Medications contraindicated on nortriptyline or escitalopram. These include:

1. 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

2. 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 disopryamide), the antihistamines astemizole, mizolastine, the antimicrobial agents sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, anti-malarian treatment),and some antiretrovirals

7. 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

8. Treatment with antiparkinsonian medication should be optimized and stable within 4 weeks of screening and with no plans to change up to primary endpoint (8 weeks)

9. Participation in another clinical trial of an investigational medicinal product or device within the last 30 days