Antidepressants Trial in Parkinson's Disease (ADepT-PD)

DESIGN Multicentre, parallel-group, 3-arm RCT with internal pilot study SETTING Parkinson’s disease clinics in the UK supported by the CLRN and the UK Parkinson’s Excellence Networks and linked with the Tracking-PD study TARGET POPULATION Patients with Parkinson's disease with depressive disorder INCLUSION CRITERIA Diagnosis of idiopathic PD according to the UK Brain Bank criteria; aged 18 to 85 years; DSM V diagnosis of a depressive disorder and BDI-II score >/=14 EXCLUSION CRITERIA Women who are pregnant, breastfeeding or of childbearing potential without effective contraception; patients not able to read or to complete self-rating questionnaires; no patients will be excluded based on PD motor severity, but patients unable to communicate answers to outcome measures will be excluded; patients with minimental state examination score <21 or unable to give consent; mood fluctuations related predominantly to off-periods; treatment with an SSRI or TCA within 4 weeks of enrolment; contraindications to nortriptyline and/or escitalopram Treatment with antiparkinsonian medication should be optimized and stable within 4 weeks of inclusion and with no plans to change up to primary endpoint INTERVENTION Nortriptyline (target dose 100mg), escitalopram (target dose 20mg) or placebo, in addition to available standard psychological care OUTCOME MEASURES Primary BDI II at 8 weeks of treatment. The BDI-II is a patient-completed scale that has been shown to be valid, sensitive and responsive in patients with PD Secondary Clinically significant adverse events and number of drop-outs; Toronto Side Effects Scale; Falls diary; MDS-UPDRS scale; levodopa-equivalence dose; EQ-5D-5L; Shortened Client Service Receipt Inventory; ICECAP capability index measure; Carer EQ-5D-SL and Carers QoL Questionnaire Parkinsonism; Patient-reported Global Clinical Impression scale (CGI); Montreal Cognitive Assessment (MoCA); Parkinson Anxiety Scale; SCOPA-sleep; Demographic data, comorbidities, medication modified; assessment of participant’s awareness of allocated treatment arm; repeat assessments at 26 and 52-weeks SAMPLE SIZE At 90% power and a significance level of 0.025 (to account for multiple comparisons) we require 113 per group to detect a 3-point BDI II difference [SD for change 6.35] for the escitalopram–placebo and the nortriptyline–placebo comparisons at 8 weeks. Allowing for 20% attrition, 136 will need to be recruited per arm (n=408 overall). For the estimation of adverse events, a trial with 136 subjects in each experimental condition will provide 95% confidence intervals on the comparison between active agents ±12% when the rate of events is around 50%, and ±7% when the rate of events is around 10%. TRIAL DURATION 47 months, including a 24 months recruitment period (including 6 months internal Pilot study), with a double-blind trial duration per participant of 8 weeks to primary endpoint and of 52 weeks to secondary endpoint. STOP CRITERIA If recruitment 30%. Loss to follow up before primary outcome >20%. Adherence to trial medication <60%. PPI INVOLVEMENT The study will receive strong input from our PPI members throughout the study, in advising on and reviewing study methods and materials, engagement, monitoring of the study, and dissemination.