Depression in patients with Parkinson's disease Mental and Behavioural Disorders
Conditions
Interventions
Current interventions as of 27/04/2023:
Method of randomisation: Stratified randomisation will be performed with strata defined by site and depression severity (BDI-II 0-19/20-63).
Patients will be
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 27/04/2023: 1. Patients with a diagnosis of idiopathic PD, based on a history and neurological exam performed by the enrolling investigator with presence of at least two of the three cardinal signs of PD: rigidity, bradykinesia, and rest tremor with no evidence of diagnostic alternatives. 2. Aged 18 years old or above 3. Fulfilling operationally defined subsyndromal depression (presence of two or more depressive symptoms at threshold or subthreshold levels, at least one of which had to include depressed mood or anhedonia or diagnostic (DSM-V) criteria for a depressive disorder (i.e. major depressive disorder or persistent depressive disorder)). 4. Beck Depression Inventory-II (BDI-II) score =14. 5. Written informed consent provided. 6. 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). _____ Previous inclusion criteria: 1. Patients with a diagnosis of idiopathic PD, based on a history and neurological exam performed by the enrolling investigator with presence of at least two of the three cardinal signs of PD: rigidity, bradykinesia, and rest tremor with no evidence of diagnostic alternatives 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
Exclusion criteria: Current exclusion criteria as of 27/04/2023: 1. Women who are pregnant, breastfeeding or of childbearing potential without effective contraception (hormonal or barrier method of birth control; or abstinence). Periodic abstinence (e.g.calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 2. Patients who do not have sufficient understanding of the English language to be or are not able to understand the Patient Information Sheet or the self-completed questionnaires or patients who are unable to communicate answers to the self-rating questionnaires. 3. Patients with Montreal Cognitive Assessment (MoCA) score 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. 8. 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. 9. Participation in another clinical trial of an investigational medicinal product or device within the last 30 days of randomisation. 10. Any clinical condition which in the opinion/ clinical judgement of the investigator would make the patient unsuitable for the trial due to safety concerns. _____ Previous 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 who do not have sufficient understanding of the English language to be able to read and understand the self-completed questionnaires or patients who are unable 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. These include: a. Patients with known QT-interval prolongation or congenital long QT syndrome. b. Recent myocardial infarction, any degree of heart block or other cardiac arrhythmias 6. Medications contraindicated on nor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Depressive symptoms measured using the Beck Depression Inventory (BDI-II) at 8 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured at 8, 26 and 52 weeks of treatment: Patient-reported outcomes: 1. Level of depression measured using the Becks Depression Inventory (BDI-II) at weeks 26 and 52 2. Level of depression measured using the Patient Health Questionnaire (PHQ9) 3. Number of participants experiencing side effects (adverse reactions) on the Modified Toronto Side Effects Scale and reporting of other adverse events 4. Anxiety symptoms measured using the Parkinson Anxiety Scale 5. Quality of life measured using the EQ-5D-5L questionnaire 6. Capability measured using the ICECAP-O questionnaire 7. Health and social care resource use measured using the modified Client Service Receipt Inventory (CSRI) 8. Time spent by paid carers measured using a modified version of the iMTA Valuation of Informal Carers Questionnaire (iVICQ) (asked alongside the CSRI) 9. Changes in concomitant medication Clinician and patient-reported outcomes: 1. Motor and non-motor experiences measured using the MDS-UPDRS69 Part I and II, and motor examination and motor complications measured using the MDS-UPDRS Part III and IV (including a recording of the participant’s movements) Clinician-reported outcomes: 1. Cognitive function measured using the Montreal Cognitive Assessment (MoCA) 2. Overall clinical effectiveness measured using the Global Clinical Impression scale (CGI) - change in health question 3. Levodopa-equivalence dose 4. Number of drop-outs Carer-reported outcomes: The trial does not require that the participants have a carer, however, if a participant does have a carer, the carer will be asked if they agree to complete the following questionnaires: 1. Carer’s quality of life measured using the EQ-5D-5L63-64 and Carers Quality of Life Questionnaire for Parkinsonism 2. Impact on informal carers measured using a modified version of the iVICQ68 (asked alongside the CSRI) | — |
Countries
England, United Kingdom
Outcome results
None listed